Cathepsin D Content in Colorectal Cancer

Cathepsin D content and activity were determined in matched paired sets of colorectal tumor tissue and normal mucosa and correlated with a number of biological and clinical parameters. Significantly higher cathepsin D activity was measured in tumor cytosol compared to paired normal mucosa (p < 0.02), in Dukes’ stage A tumors compared to Dukes’ B and C (p < 0.05), in tumors < 5 cm compared to those > 5 cm, or in tumors with a low proliferation rate compared to those with a high proliferation rate (p < 0.05). Moreover, significant differences in enzyme activity between tumor tissue and paired normal mucosa were observed in node-positive and G2 tumors (p < 0.05). No significa…

P1.13-16 The Diagnostic Accuracy of Circulating Tumor DNA for the Detection of EGFR-T790M Mutation in NSCLC: A Systematic Review and Meta-Analysis

The role of polymorphisms occurring in BRCA1/2 genes in determining ovarian cancer risk.

e17551 Background: Ovarian cancer (OC) is the 10th tumor occurring in women, it accounts for 30% of all malignant tumor affecting female genital tract in Italy. There are several factors that contribute to OC development; in 15-25% of cases family history of breast and ovarian cancer represent the main risk factor. It is well known that pathogenic variants (PVs) occurring in BRCA1/2 genes strongly increase the risk of developing OC, ranging from 50% in BRCA1 PVs carriers to 30% in BRCA2 PVs carriers. Recently genetic polymorphism has been shown to increase cancer risk, consequently polymorphisms in BRCA1/2 genes could represent low penetrance susceptibility alleles and contribute to determ…

Reply to: Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials (Galvano et al., J Bone Oncol 2019; 18:100252)

MicroRNAs in Colorectal Cancer Drug Resistance: Shooters become Targets

Copyright: © 2013 Fanale D, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. MicroRNAs (MiRNAs) are involved in the regulation of several biological processes such as development, differentiation, metabolism, apoptosis and proliferation. Recently, it has been shown that deregulated expression of miRNAs are present in different human cancers, suggesting a potential role in carcinogenesis [1,2]. Recent evidence suggests that miRNAs may represent potential new therapeutic approaches in patients with dru…

DNA aneuploidy, high SPF and specific p53 mutations are independent prognostic factors in colorectale cancer (CRC)

The role of Aurora-A inhibitors in cancer therapy

Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by pa…

Downregulated expression of Cdc25A gene in MCF-7 breast cancer cell

Is BRCA1-5083del19, identified in breast cancer patients of Sicilian origin, a Calabrian founder mutation?

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…

DNA-aneuploidy and high SPF and specific p53 mutations are independent prognostic factors in colorectal cancer (CRC).

Significance of P16INK4A hypermethylation gene in primary head/neck and colorectal tumors: it is a specific tissue event? Results of a 3-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study

Background Methylation of the p16 promoter is one of the most frequent mechanisms of gene inactivation; its incidence is extremely variable according to the type of tumor involved. Our purpose was to analyze the hypermethylation of the p16 promoter in laryngeal squamous cell carcinomas (LSCC), salivary gland (SG) tumors and in colorectal cancer (CRC), to detect any possible association with the clinicopathological features and to determine the prognostic significance of the p16 gene in the tumors analyzed. Patients and methods The hypermethylation of the p16 promoter was prospectively analyzed, by MSP, in a consecutive series of 64 locally advanced LSCC patients, in a consecutive series of …

The Genetics of Breast Cancer

Breast cancer (BC) is a complex and heterogeneous disease caused by interaction of both genetic and nongenetic risk factors. The biological diversity of sporadic BCs consists in the development of several BC subtypes, which are systematically different from one another and which present specific genetic and phenotypic features. Recently, with the advent of cDNA microarrays it has been possible to associate a distinctive “molecular portrait” to a single BC subtype and, consequently, improve BC taxonomy. From a clinical point of view, the gene expression profiles could supply the classic pathological experiment with the aim to select patients with a better prognosis and that could have a bene…

Advanced breast cancer at presentation (ABC-p) in octogenarian women (OW): Specific elderly-devoted risk tests(SEDRT) (CARG+CRASH) as new tools to prevent serious/irreversible adverse reactions (AR) in frail patients.

e12510 Background: Due to current lengthening of average lifespan and progressive increase of malignant tumors in mankind, more new strategies must be constantly sought especially for thirdage neoplasms. Nevertheless because severe toxicity developed in the majority of frail patients, administration of therapy may cause high risk of life-threatening AIM: We have considered in this paper ABC in frail patients like OW. Purpose of the study is preliminary detection of the overall toxicity (OTox) through the possible use of specifics tests adopted specially in frail patients such as OW, to ensure greater control in drugs administration with good effectiveness. AIM: We have considered in this p…

TP53 Mutation in exon 5 and S-Phase Fraction but not Mutations in Ras gene family and DNA-ploidy are Indipendent prognostic indicators in Laryngeal Squamous Cell Carcinoma

BRCA1 and BRCA2 variants of uncertain clinical significance and their implications for genetic counseling

Moving the target on the optimal adjuvant strategy for resected pancreatic cancers: A systematic review with meta-analysis

Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studie…

Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Background: The addition of PD-L1 inhibitors to platinum-based chemotherapy (CT) has newly received United States Food and Drug Administration (FDA) approval in extensive stage-small cell lung cancer (ES-SCLC). PD-1 agents similarly improved survival rates, even if not yet supported by international regulatory agencies. The current work aims to assess different efficacy and safety profiles among chemoimmunotherapy plus immuno-oncology (CT+IO) approaches according to different immune checkpoint inhibitor (ICI) subtypes. Material & Methods: We included in our meta-analysis six first-line randomised controlled trials (RCTs) comparing the association of single-agent ICI with CT versus CT al…

How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF an…

P2.04-10 Early Monitoring of Blood Biomarkers to Predict Nivolumab Efficacy in NSCLC Patients

Fattori Predittivi di Risposta ai Citostatici nei Tumori del Tratto Gastrointestinale

The TP53 colorectal cancer international collaborative study on the prognostic and predictive significance of p53 mutation: influence of tumor site, type of mutation, and adjuvant treatment

Purpose The aims of the TP53 Colorectal Cancer (CRC) International Collaborative Study were to evaluate the possible associations between specific TP53 mutations and tumor site, and to evaluate the prognostic and predictive significance of these mutations in different site, stage, and treatment subgroups. Patients and Methods A total of 3,583 CRC patients from 25 different research groups in 17 countries were recruited to the study. Patients were divided into three groups according to site of the primary tumor. TP53 mutational analyses spanned exons 4 to 8. Results TP53 mutations were found in 34% of the proximal colon tumors and in 45% of the distal colon and rectal tumors. They were assoc…

Body mass index and baseline platelet count as predictive factors in Merkel cell carcinoma patients treated with avelumab

BackgroundMerkel cell carcinoma (MCC) is a rare and aggressive skin cancer, associated with a worse prognosis. The Immune Checkpoint Inhibitors (ICIs) avelumab and pembrolizumab have been recently approved as first-line treatment in metastatic MCC (mMCC). The clinical observation of improved outcomes in obese patients following treatment with ICIs, known as the “obesity paradox”, has been studied across many types of tumors. Probably due to the rarity of this tumor, data on mMMC patients are lacking.Patients and methodsThis is an observational, hospital-based, study to investigate the role of Body Mass Index (BMI) as predictive biomarker of ICI response in mMCC patients treated with aveluma…

Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations

Analysis of the genetic status of Ki-ras and p53 in primary colorectal carcinomas and matched colorectal liver metastasis from 30 patients reveals an overall heterogeneity both within and between the two tumoral tissues. Both genes were found mutated with a similar frequency in both tissues; however, identical mutations in primary tumor and matched metastasis were found less frequently in the case of the Ki-ras than the p53 gene. Only in three cases the same p53 and Ki-ras mutations found in the primary tumor were found also in the metastasis. In several metastatic specimens the DNA bearing a mutation detected also in the primary tumor appears significantly less abundant than the wild-type …

sj-docx-14-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-14-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-pdf-1-tam-10.1177_1758835920975326 – Supplemental material for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Supplemental material, sj-pdf-1-tam-10.1177_1758835920975326 for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients by Lorena Incorvaia, Daniele Fanale, Marco Bono, Valentina Calò, Alessia Fiorino, Chiara Brando, Lidia Rita Corsini, Sofia Cutaia, Daniela Cancelliere, Alessia Pivetti, Clarissa Filorizzo, Maria La Mantia, Nadia Barraco, Stefania Cusenza, Giuseppe Badalamenti, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

4843delC of the BRCA1 gene is a possible founder mutation in Southern Italy (Sicily).

Various studies have been published in Italy regarding the different BRCA1 mutations, but only the BRCA1-5083del19 mutation is recurrent and specific to individuals of Italian descent with a founder effect on the Calabrian population. In our previous study, BRCA1-5083del19 mutation carriers were found in four index cases of 106 Sicilian patients selected for familial and/or hereditary breast/ovarian cancers. The high frequency rate of this mutation identified in the Sicilian population led us to perform haplotype analysis in all family carriers. Five highly polymorphic microsatellite markers were used (D17S1320, D17S932, D17S1323, D17S1326, D17S1325) to establish whether or not all these fa…

The prognostic impact of tumor mutational burden (TMB) in the first-line management of advanced non-oncogene addicted non-small-cell lung cancer (NSCLC): a systematic review and meta-analysis of randomized controlled trials

Background The role of tumor mutational burden (TMB) is still debated for selecting advanced non-oncogene addicted non-small-cell lung cancer (NSCLC) patients who might benefit from immune checkpoint inhibitors (ICIs). Of note, TMB failed to predict a benefit in overall survival (OS) among such patients. Materials and methods The purpose of this meta-analysis was to compare efficacy outcomes among first-line immune-oncology (IO) agents versus standard platinum-based chemotherapy (CT) within two subgroups (TMB-low and TMB-high on either tissue or blood). We collected hazard ratios (HRs) to evaluate the association for progression-free survival (PFS) and OS, with the relative 95% confidence i…

Are Long Noncoding RNAs New Potential Biomarkers in Gastrointestinal Stromal Tumors (GISTs)? The Role of H19 and MALAT1

Long noncoding RNAs (lncRNAs) are emerging as key regulators of genetic and epigenetic networks, and their deregulation may underlie complex diseases, such as carcinogenesis. Several studies described lncRNA alterations in patients with solid tumors. In particular, HOTAIR upregulation has been associated with tumor aggressiveness, metastasis, and poor survival in gastrointestinal stromal tumor (GIST) patients. We analyzed expression levels of other lncRNAs, H19 and MALAT1, in FFPE tissue specimens from 40 surgically resected and metastatic GIST patients, using real-time PCR analysis. H19 and MALAT1 were both upregulated in 50% of GIST patients. MALAT1 lncRNA expression levels seem to be cor…

HepatomiRNoma: The proposal of a new network of targets for diagnosis, prognosis and therapy in hepatocellular carcinoma

Abstract: The diagnosis and treatment of hepatocellular carcinoma (HCC) underwent a huge advancement in the last years. Recently, microRNAs (miRNAs) have been also studied to provide a new tool for early diagnosis of high risk patients, for prognostic classification to identify those patients who benefit cancer treatment and for predictive definition to select the right targeted drug. In this review we revised all the available data obtained to explore the role of miRNAs in HCC. This analysis led to identification of miRNAs which could gain a diagnostic, prognostic or predictive role. The results of studies on miRNAs involved in HCC are initial and far from providing scientific evidences to…

Abstract 1855: Role of mTOR inhibition in triple-negative breast cancer

Abstract BACKGROUND: Triple-negative breast cancers (TNBC) represent the 10-17% of all diagnosed breast cancers (BC) and are characterized by the absence of ER/PgR expression, HER2 amplification and often show a basal-like phenotype. TNBC are often diagnosed in patients with BRCA1 germline mutation and unfortunately treatment options are still limited. The mTOR (Mammalian Target Of Rapamycin) pathway seems to play an important role in BC pathogenesis and it is possible to target this pathway by inhibitors such as rapamycin. In human BC cross talk between ER/PgR receptors signaling and the mTOR pathway is believed to be responsible for resistance to hormone therapy probably due to a down reg…

Role of K-RAS and P53 Gene in Salivary Glands Tumorigenesis

Technical Aspects for the Evaluation of Circulating Nucleic Acids (CNAs): Circulating Tumor DNA (ctDNA) and Circulating MicroRNAs

Circulating nucleic acids (CNAs), for example, circulating tumor DNA (ctDNA) and circulating microRNA (miRNA), represent promising biomarkers in several diseases including cancer. They can be isolated from many body fluids, such as blood, saliva, and urine. Also ascites, cerebrospinal fluids, and pleural effusion may be considered as a source of CNAs, but with several and intrinsic limitations. Therefore, blood withdrawal represents one of the best sources for CNAs due to the very simple and minimally invasive way of sampling. Moreover, it can be repeated at different time points, giving the opportunity for a real-time monitoring of the disease.

Farmacogenomica nei carcinomi colorettali: prospettive nella terapia personalizzata

Metastatic site location influences the diagnostic accuracy of ctDNA EGFR- mutation testing in NSCLC patients: a pooled analysis

Background: Recent studies evaluated the diagnostic accuracy of circulating tumor DNA (ctDNA) analysis in the detection of epidermal growth factor receptor (EGFR) mutations from plasma of NSCLC patients, overall showing a high concordance as compared to standard tissue genotyping. However it is less clear if the location of metastatic site may influence the ability to identify EGFR mutations. Objective: This pooled analysis aims to evaluate the association between the metastatic site location and the sensitivity of ctDNA analysis in detecting EGFR mutations in NSCLC patients. Methods: Data from all published studies, evaluating the sensitivity of plasma-based EGFRmutation testing, stratifi…

sj-docx-12-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-12-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Y179C, F486L and N550H are BRCA1 variants that may be associated with breast cancer in a Sicilian family: results of a 5-year GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

Background Over 600 different pathogenic mutations have been identified in the BRCA1 gene. Nevertheless, numerous missense mutations of unknown biological function still exist. Understanding of biological significance of these mutations should help in genetic counselling to carriers and their families. Patients and methods A total of 104 patients with breast and/or ovarian cancer whose genetic counselling answered the criteria of the American Society of Clinical Oncology (ASCO 2003), were prospectively screened for mutations in all coding exons of the BRCA1 gene by automatic direct sequencing. Results During these mutational screening procedures one case presented three mutations classified…

Galectin-3 in acute coronary syndrome

Acute coronary syndrome (ACS) is a very common cause of hospitalizations worldwide each year. In the past decades biomarkers have become an indispensable tool for diagnosis, risk stratification and prognosis of cardiovascular disease, including ACS. Despite Troponin is considered the gold standard in diagnosis of ACS, several molecules have been investigated to identify predictive biomarkers of prognosis. Among these, Gal-3 has emerged as a promising prognostic marker. It has a pivotal role in inflammation and fibrosis. Both experimental and clinical studies have shown Gal-3 is an independent predictor of all-cause mortality, cardiovascular death and occurrence of HF following ACS. This art…

Analysis of tissue and circulating microRNA expression during metaplastic transformation of the esophagus

Genetic changes involved in the metaplastic progression from squamous esophageal mucosa toward Barrett's metaplasia and adenocarcinoma are almost unknown. Several evidences suggest that some miRNAs are differentially expressed in Barrett's esophagus (BE) and esophageal adenocarcinoma. Among these, miR-143, miR-145, miR-194, miR-203, miR-205, miR-215 appear to have a key role in metaplasia and neoplastic progression. The aim of this study was to analyze deregulated miRNAs in serum and esophageal mucosal tissue biopsies to identify new biomarkers that could be associated with different stages of esophageal disease. Esophageal mucosal tissue biopsies and blood samples were collected and analyz…

Pharmacogenomics in colorectal carcinomas: Future perspectives in personalized therapy

The recent introduction of new drugs such as capecitabine, irinotecan, and oxaliplatinum has greatly improved the clinical outcome of patients with advanced/metastatic colorectal cancer. Nevertheless, some patients may suffer from the adverse drug reactions which will probably be the main cause of chemotherapy failure. The goal of pharmacogenomics is to find correlations between therapeutic responses to drugs and the genetic profiles of patients; the different responses to a particular drug are due, in fact, not only to the specific clinico-pathological features of the patient or to environmental factors, but also to the ethnic origins and the particular individual's genetic profile. Genes …

Specific codon 13 K-ras mutations are predictive of clinical outcome in colorectal cancer patients, whereas codon 12 K-ras mutations are associated with mucinous histotype

Background: K-ras mutations, one of the earliest events observed in colorectal carcinogenesis, are mostly found in codons 12 and 13, and less frequently in codon 61, all three of which are estimated to be critical for the biological activity of the protein. Nevertheless the prognostic significance of such mutations remains controversial. Our purpose was to assess whether any or specific K-ras mutations in primary colorectal cancer had prognostic significance and were linked to clinico-pathological parameters. Patients and methods: Paired tumor and normal tissue samples from a consecutive series of 160 untreated patients (median of follow up 71 months), undergoing resective surgery for prima…

Analysis of TP53, Ki-Ras and P16INK4A promoter methylation as potential prognostic factors in patients with colorectal cancer

Hypoxia and Human Genome Stability: Downregulation of BRCA2 Expression in Breast Cancer Cell Lines

Previously, it has been reported that hypoxia causes increased mutagenesis and alteration in DNA repair mechanisms. In 2005, an interesting study showed that hypoxia-induced decreases in BRCA1 expression and the consequent suppression of homologous recombination may lead to genetic instability. However, nothing is yet known about the involvement of BRCA2 in hypoxic conditions in breast cancer. Initially, a cell proliferation assay allowed us to hypothesize that hypoxia could negatively regulate the breast cancer cell growth in short term in vitro studies. Subsequently, we analyzed gene expression in breast cancer cell lines exposed to hypoxic condition by microarray analysis. Interestingly,…

The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal

Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGF…

BRCA1 and BRCA2 germline mutations in sicilian breast and/or ovarian cancer families and their association with familial profiles

EGF Induces STAT3-Dependent VEGF Expression in HT-29 colon cancer cells

Safety and effectiveness of gemcitabine for the treatment of classic Kaposi’s sarcoma without visceral involvement

Background: Classic Kaposi’s sarcoma (CKS) is a rare, multifocal, endothelial cell neoplasm that typically occurs in elderly people with previous infection by human herpes virus-8. Prospective trials are rare, and the choice of drugs relies on prospective trials performed on HIV-associated Kaposi’s sarcoma (KS). Pegylated liposomal anthracyclines and taxanes are considered the standard first- and second-line chemotherapy, respectively. Despite the indolent biologic behavior, the natural history is characterized by recurrent disease. This condition of chronic administration of cytotoxic drugs is often associated with immediate/long-term adverse events. Methods: This was an observational, ret…

1543P Gemcitabine in classic Kaposi’s sarcoma: A pilot study

sj-docx-7-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-7-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

TP53 mutations are not prognostic indipendent indicators in bladder cancer

The prognostic role of TP53 mutations in advanced laryngeal squamous cell carcinoma (LSCC).

502P Impact of different selection approaches for identifying Lynch syndrome-related colorectal cancer patients

A new germline mutation in BRCA1 gene in a sicilian family with ovarian cancer

A group of 103 sicilian patients with hereditary and familiar breast and/or ovarian cancer were screened for Breast Cancer 1 gene (BRCA1) mutations by direct sequencing PCR products spanning the coding region and partial intronic regions of the BRCA1 gene. In this study, we report a new germline mutation in BRCA1 gene, not previously reported in the BIC database, in a woman with ovarian cancer at 46 years old. Mother's proband has been diagnosed the same histotype of ovarian cancer at 42 age. The mutational analyses that shown a 4843delC frameshift mutation in exon 16 of BRCA1 gene was extended to other family members including the proband's brother and her two sons. Direct automatic sequen…

Prognostic significance of p16INK4a alterations and 9p21 loss of heterozigosity in locally advanced laryngeal squamous cell carcinoma

The p16INK4a gene, localized within chromosome 9p21, has been identified as a cyclin-dependent kinase inhibitor and may negatively regulate the cell cycle acting as a tumor suppressor. Genetic alterations involving the 9p21 region are common in human cancers. A consecutive series of 64 untreated patients (median of follow up 53 months) undergoing surgical resection for locally advanced laryngeal squamous-cell carcinomas (LSCCs) has been studied prospectively. Our purpose was to investigate p16 alterations (9p21 allelic loss, hypermethylation and point mutations) and their possible association with clinico-pathological data and flow cytometric variables (DNA-ploidy and S-phase fraction (SPF)…

Analysis of Ki-ras mutations in stage I rectal carcinomas and respective regional lymphonodes

Cell-free DNA and exoDNA analysis in metastatic colorectal cancer patients (mCRC).

e16093 Background: Liquid biopsy is a growing field in translational cancer research. Two of the most studied liquid biopsy biomarkers are cell-free DNA (cfDNA) and exosomes, nano-sized vesicles that transport protein and nucleic acids including DNA (exoDNA). Therefore, both cfDNA and exoDNA are potentially useful to investigate the molecular landscape of tumor with a minimally invasive approach. Here we investigate the prognostic and predictive role of both cfDNA and exoDNA in mCRC using Next Generation Sequencing (NGS) analysis. Methods: From July 2017 to September 2018, samples of 40 mCRC patients were collected at the Medical Oncology of the AOUP Paolo Giaccone of Palermo. Blood sample…

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

Item does not contain fulltext BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified ac…

Eribulin (E) and capecitabine (C), a combined treatment schedule in elderly metastatic breast cancer (EMBC): Efficacy and safety evaluation (E&amp;S).

e20513 Background: E mesylate, a nontaxane microtubule dynamics inhibitor, was approved in the U.S in 2010 for the treatment of MBC who have previously received at least 2 MBC chemo regimens, inclu...

Oncogene Addiction in Solid Tumors

The term “oncogenic addiction” refers to the phenomenon by which tumor cells become completely dependent on a single pathway, derived from the activation of a specific oncogene, for their survival and proliferation. The clinical relevance of oncogene addiction paradigm is highlighted by a growing number of examples that demonstrate the efficacy of several therapeutic agents that target specific oncogenes in various cancer types. This chapter aims to summarize the recent evidences concerning the concept of oncogene addiction and describes molecular mechanisms that could explain this phenomenon.

TP53 in gastric cancer: mutations in the l3 loop and LSH motif DNA-binding domains of TP53 predict poor outcome.

The aim of this study was to clarify whether specific p53 mutations may have biological relevance in terms of disease relapse or death in gastric carcinomas (GC). Resected specimens from a consecutive series of 62 patients with GC undergoing potentially curative surgery were prospectively studied. The mutational status of exons 5-8 of the p53 gene was investigated in 62 cases using the PCR-SSCP and sequencing. Presence of microsatellite instability (MSI) was evaluated in 56 cases by analyzing loci highly sensitive of MSI. Twenty mutations of p53 were detected in 17 of the 62 cases analyzed (27%). Ten mutations (50%) occurred in highly conserved domains. According to the p53 specific functio…

Immunotherapy for recurrent ovarian cancer: a further piece of the puzzle or a striking strategy?

Introduction: Treatment of ovarian cancer has been long standardized with the inclusion of surgery and chemotherapy based on platinum and taxanes, this strategy reaching high remission rates. However, when this treatment fails, further options are available with little benefit. Since ovarian cancer has specific immunologic features, actually immunotherapy is under evalua- 15 tion to overcome treatment failure in patients experiencing recurrence. Areas covered: Immunogenicity of ovarian cancer and its relationship with clinical outcomes is briefly reviewed. The kinds of immunotherapeutic strategies are summarized. The clinical trials investigating immunotherapy in recurrent ovarian cancer pa…

Genetic and Molecular Characterization of The Human Osteosarcoma 3AB-OS Cancer Stem Cell Line: A Possible Model For Studying Osteosarcoma Origin and Stemness

Finding new treatments targeting cancer stem cells (CSCs) within a tumor seems to be critical to halt cancer and improve patient survival. Osteosarcoma is an aggressive tumor affecting adolescents, for which there is no second-line chemotherapy. Uncovering new molecular mechanisms underlying the development of osteosarcoma and origin of CSCs is crucial to identify new possible therapeutic strategies. Here, we aimed to characterize genetically and molecularly the human osteosarcoma 3AB-OS CSC line, previously selected from MG63 cells and which proved to have both in vitro and in vivo features of CSCs. Classic cytogenetic studies demonstrated that 3AB-OS cells have hypertriploid karyotype wit…

GENOTYPE ANALYSIS OF COLORECTAL CARCINOMAS THROUGH LASER PRESSURE CATAPULTING (LPC)

Caretakers and Gatekeepers

It has now been generally accepted that the genes responsible for familial cancer syndromes can be divided into two categories, known as caretakers and gatekeepers. Caretakers are genes that control the maintenance of the genetic information integrity in each cell while gatekeepers are those genes which directly regulate tumor growth, codifying for proteins which either stimulate or inhibit proliferation, differentiation or apoptosis. Keywords: gatekeeper genes; caretaker genes; tumor suppressor genes; cell cycle; hereditary syndromes

sj-docx-3-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-3-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

1281P The prognostic impact of tissue tumour mutational burden (TMB) in the first-line treatment of advanced non-oncogene addicted non-small cell lung cancer (NSCLC): A systematic review and meta-analysis of randomized controlled trials

Ramucirumab and its use in gastric cancer treatment

Abstract: The inhibition of the mechanisms of tumor neo-angiogenesis represents a milestone that in the last 10 years has seen the advent of numerous molecules to target action against the vascular endothelial growth factor (VEGF). More recently, new molecules have been developed that inhibit tumor spread by the blockade of specific VEGF receptors (VEGFRs), thereby preventing the binding of a ligand to its receptor and the cascade of proliferative events downstream. Ramucirumab is a fully humanized IgG1 monoclonal antibody that performs its action by blocking the isoform 2 of the VEGF receptor (VEGFR-2). Numerous preclinical and clinical studies have demonstrated its activity in several sol…

Targeting apoptosis in solid tumors: the role of bortezomib from preclinical to clinical evidence.

The ubiquitin-proteasome pathway is the main proteolytic system present in the nucleus and cytoplasm of all eukaryotic cells. Apoptosis activation induced by ubiquitin-proteasome pathway inhibition makes the proteasome a new target of anticancer therapy. Bortezomib is the first proteasome inhibitor to be approved by the US FDA; in 2003 as a third line and in 2005 as a second line therapy for the treatment of multiple myeloma only. This review focuses on the use of bortezomib, not only in its therapeutic role but also, more specifically, in its biologic role and discusses the most recent applications of the drug in solid tumors, both at a preclinical and clinical level.

Prognostic Role of Plasma PD-1, PD-L1, pan-BTN3As and BTN3A1 in Patients Affected by Metastatic Gastrointestinal Stromal Tumors: Can Immune Checkpoints Act as a Sentinel for Short-Term Survival?

Gastrointestinal stromal tumors (GISTs) represent 1% of all primary gastrointestinal tumors. Immune surveillance is often overcome by cancer cells due to the activation of immunoregulatory molecules such as programmed death protein (PD-1) and its ligand PD-L1, and butyrophilin sub-family 3A/CD277 receptors (BTN3A). Because several studies demonstrated that tumor PD-1 and PD-L1 expression may have a prominent prognostic function, this investigation aimed to discover if soluble forms of these molecules may be useful in predicting survival of metastatic GIST (mGIST) patients. Through specific ad hoc developed ELISA assays not yet available on the market, the circulating PD-1, PD-L1, BTN3A1, an…

BRCA 1/2 GENES MUTATIONAL SCREENING IN SICILIAN BREAST AND/OR OVARIAN CANCER FAMILIES

Role of the HIPPO pathway as potential key player in the cross talk between oncology and cardiology.

The HIPPO pathway (HP) is a highly conserved kinase cascade that affects organ size by regulating proliferation, cell survival and differentiation. Discovered in Drosophila melanogaster to early 2000, it immediately opened wide frontiers in the field of research. Over the last years the field of knowledge on HP is quickly expanding and it is thought will offer many answers on complex pathologies. Here, we summarized the results of several studies that have investigated HP signaling both in oncology than in cardiology field, with an overview on future perspectives in cardiology research.

Analysis of systemic inflammatory biomarkers in neuroendocrine carcinomas of the lung: prognostic and predictive significance of NLR, LDH, ALI, and LIPI score

Background: Lung neuroendocrine carcinoma (NEC) is characterized by aggressive clinical behavior and lack of treatment advances. We evaluate the prognostic and the predictive roles of systemic inflammatory biomarkers in patient circulating blood: neutrophil–lymphocyte ratio (NLR), lactate dehydrogenase (LDH), advanced lung cancer inflammation index (ALI), and the Lung Immune Prognostic Index (LIPI) score. Methods: A total of 120 patients with small-cell lung cancer (SCLC) ( n = 110) and large cell neuroendocrine carcinoma (LCNEC) ( n = 10) were enrolled. Overall survival (OS) was evaluated by Kaplan–Meier estimator and univariate and multivariate Cox proportional hazard analyses were perfor…

Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells.

Both leptin and vascular endothelial growth factor (VEGF) are growth and angiogenic cytokines that are upregulated in different types of cancer and have been implicated in neoplastic progression. Here we investigated the molecular mechanism by which leptin and VEGF expression are regulated in colon cancer by epidermal growth factor (EGF). In colon cancer cell line HT-29, EGF induced the binding of signal transducer and activator transcription 3 (STAT3) to STAT3 consensus motifs within the VEGF and leptin promoters and stimulated leptin and VEGF mRNA and protein synthesis. All these EGF effects were significantly blocked when HT-29 cells were treated with an inhibitor of the phosphoinositide…

Triple negative breast cancer: shedding light onto the role of pi3k/akt/mtor pathway

// Daniela Massihnia 1,* , Antonio Galvano 1,* , Daniele Fanale 1 , Alessandro Perez 1 , Marta Castiglia 1 , Lorena Incorvaia 1 , Angela Listi 1 , Sergio Rizzo 1 , Giuseppe Cicero 1 , Viviana Bazan 1 , Sergio Castorina 2,3,** and Antonio Russo 1,** 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 3 Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy * These authors have contributed equally to this work ** Both the authors are last name Correspondence to: Antonio Russo, email: // Keywords : ER, HER2, PI3K/AKT/mTOR inhib…

Prognostic and Predictive Role of Tumor-Infiltrating Lymphocytes (TILs) in Ovarian Cancer

In the last decade, tumor-infiltrating lymphocytes (TILs) have been recognized as clinically relevant prognostic markers for improved survival, providing the immunological basis for the development of new therapeutic strategies and showing a significant prognostic and predictive role in several malignancies, including ovarian cancer (OC). In fact, many OCs show TILs whose typology and degree of infiltration have been shown to be strongly correlated with prognosis and survival. The OC histological subtype with the higher presence of TILs is the high-grade serous carcinoma (HGSC) followed by the endometrioid subtype, whereas mucinous and clear cell OCs seem to contain a lower percentage of TI…

Hereditary Cancers and Genetics

The study of hereditary syndromes is fundamentally based on the finding and identification of susceptibility genes underlying the pathology. Although hereditary tumors account for only a small fraction of all the tumors, the knowledge of underlying genetics changed the clinical management of affected patients and their families, also providing important information on the molecular mechanisms involved in the development of sporadic tumors. In the subjects who inherit a germline mutation, all the cells of the organism are carriers of that mutation, predisposing such subject to develop neoplasm more easily and earlier compared to the general population. The identification of individuals with …

Metastatic site location may influence the diagnostic accuracy of plasma EGFR-mutation testing in NSCLC: A pooled analysis

Biomarkers as Prognostic, Predictive, and Surrogate Endpoints

The improved understanding of tumor biology associated with the recent technological advancement has revealed a growing number of potential tumor biomarkers as candidate for clinical use, providing new opportunities for improving the management of cancer patients in all phases of care. Biomarkers have several clinical applications in oncology, including risk assessment for disease recurrence or early diagnosis in healthy population. After the advent of targeted therapies, a growing interest has been focused on their potential role as prognostic, predictive, and surrogate endpoints, in order to promote personalized strategies. The introduction of molecular biomarkers in clinical practice has…

sj-docx-12-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-12-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

DNA ploidy and S-phase fraction, but not p53 or NM23-H1 expression, predict outcome in colorectal cancer patients. Result of a 5-year prospective study.

Purpose: The aim of this study was to determine TP53 and NM23-H1 immunoreactivity, DNA ploidy, and S-phase fraction (SPF) in a series of 160 patients undergoing resective surgery for primary operable colorectal cancer (CRC) and to establish whether these alterations have any clinical value in predicting CRC patients' prognosis. Methods: TP53 and NM23-H1 expressions were evaluated on paraffin-embedded tissue by immunohistochemistry and DNA-ploidy and SPF on frozen tissue by flow-cytometric analysis. Results: The median follow-up time in our study group was 71 months (range 34-115 months). P53 protein expression was associated with distal tumors (P &lt; 0.05) and DNA aneuploid tumors (P &lt; …

sj-docx-10-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-10-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

A study of a new germline mutation in BRCA1 gene in two Sicilian families: a founder mutation?

sj-docx-14-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-14-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-8-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-8-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Expression of angiogenic regulators. VEGF and leptin, is regulated by the EGF/P13K/STAT3 pathway in colorectal cancer cells

Tumor Biology and Natural History

Tumors are not uniform diseases but heterogeneous entities consisting of cell populations called cell clones, with different genetic and molecular features. The ability of a tumor to evolve and fit to host microenvironment, by developing often resistance mechanisms to the anticancer therapies, is dependent on this biological variability. In fact, the variability observed within individual tumors, known as intra-tumor heterogeneity, represents the crucial step in cancer clonal evolution process, by promoting and driving a genetic mechanism able to select the fittest cell clones. A single clonal origin is usually shown by most of tumors at the early stages of the disease, whereas advanced-sta…

BRCA 1/2 VARIANTS OF UNCERTAIN CLINICAL SIGNIFICANCE IN PATIENTS WITH FAMILIAL AND HEREDITARY BREAST/OVARIAN CANCER

KRAS and BRAF as prognostic biomarkers in patients undergoing surgical resection of colorectal cancer liver metastasis: A systematic review and meta-analysis.

3565Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of li...

P33.15 TMB in the First-Line Setting of NSCLC: A Systematic Review with Indirect Comparisons Between PD-1 and PD-L1 Inhibitors

Finding the right biomarker for renal cell carcinoma (RCC): Nivolumab treatment induces the expression of specific peripheral lymphocyte microRNAs in patients with durable and complete response

Abstract Background The variability of clinical response to immune checkpoint inhibitors in RCC patients makes necessary the discovery of predictive biomarkers for patient selection. Emerging evidence has revealed a multitude of silenced genes and deregulated signalling pathways. These findings point towards extensive microRNAs (miRNAs) regulation and imply epigenetic reprogramming as a key feature of RCC. The aim of this study was to analyze the peripheral lymphocyte miRNA expression profile in metastatic RCC patients undergoing nivolumab treatment, to identify a lymphocyte miRNA signature specifically expressed in patients with partial or complete response (RP; RC) >12 months. Methods miR…

sj-pdf-3-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-3-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

High prevalence of BRCA1 deletions in BRCAPRO-positive patients with high carrier probability.

Mutation screening of the BRCA1 and BRCA2 genes in probands with familial breast/ovarian cancer has been greatly improved by the multiplex ligation-dependent probe amplification (MLPA) assay able to evidence gene rearrangements not detectable by standard screening methods. However, no criteria for selection of cases to be submitted to the MLPA test have been reported yet. We used the BRCAPro software for the selection of familial breast/ovarian cancer probands investigated with the MLPA approach after negative BRCA1/2 conventional mutation screening. One hundred and seventy-seven probands were investigated for germline BRCA1/2 mutations after assessment of genetic risk using BRCAPro. Proban…

MUTYH-associated tumor syndrome: The other face of MAP

MUTYH gene is involved in the base excision repair (BER) mechanism and its pathogenic alterations are associated with colorectal polyposis and cancer. MUTYH-associated polyposis (MAP) is a condition which is inherited in an autosomal recessive manner. MAP patients, beyond colorectal cancer (CRC), may develop other types of tumors, including duodenal, breast, ovarian, pancreatic, bladder and skin cancers. Carriers of biallelic MUTYH likely pathogenic/pathogenic variants exhibit a high lifetime risk of CRC, though cancer risk evidence becomes less clear when monoallelic carriers and extraintestinal tumors are considered. However, several studies recently reported an increased genetic suscepti…

Laser Pressure Catapulting (LPC): Optimization LPC-System and Genotyping of Colorectal Carcinomas

Genotype analysis is becoming more and more useful in clinical practice, since specific mutations in tumors often correlate with prognosis and/or therapeutic response. Unfortunately, current molecular analytical techniques often require time-consuming and costly steps of analysis, thus making their routine clinical use difficult. Moreover, one of the most difficult problems arising during tumor research is that of their cell heterogeneity, which depends on their clear molecular heterogeneity. SSCP analysis discriminates by means of aberrant electrophoresis migration bands, mutated alleles which may represent as little as 15-20% of their total number. Nevertheless, in order to identify by se…

Patterns of DNA-ploidy in operable colorectal carcinoma: A prospective study of 100 cases

A prospective study of cellular DNA content was made by means of flow cytometry in a nonconsecutive series of 100 patients undergoing surgery for primary colorectal adenocarcinoma. DNA-aneuploidy was present in 80% of cases (80/100); 39% of these were multiclonal (31/80). There was no significant correlation between DNA-ploidy and the clinical and pathological features examined, except for the primary tumor site (right colon vs. left colon vs. rectum: P less than 0.001). After a minimum follow-up of 30 months, out of 40 patients with no local invasion and/or distant metastases, 100% (9/9) of those with DNA-diploid neoplasias showed no signs of disease relapse, vs. 55% (17/31) of the DNA-ane…

Prognostic and predictive biomarkers for targeted therapy in NSCLC: For whom the bell tolls?

Introduction: The discovery of molecular biomarkers and the advent of targeted therapies have led to a radical change in the treatment of several tumors, including NSCLC. In the last few years, the number of molecular biomarkers has rapidly increased, and a growing interest has been recently focused on their potential prognostic and predictive value in clinical settings. Areas covered: This review describes all the molecular biomarkers with prognostic and predictive value in NSCLC, including both clinically approved biomarkers, and emerging biomarkers under investigation in clinical trials. Liquid biopsy and applications of circulating biomarkers are also described. Expert opinion: The onco…

Is there any place for PD-1/CTLA-4 inhibitors combination in the first-line treatment of advanced NSCLC?—A trial-level meta-analysis in PD-L1 selected subgroups

BACKGROUND: The advent of immuno-oncology (IO) represented a breakthrough in non-small cell lung cancer (NSCLC) therapy over the last few years. However, establishing the optimal therapeutic options among programmed death-ligand 1 (PD-L1) selected subgroups still addresses an unmet need in the clinical setting. METHODS: We performed a systematic review and finally included eleven first-line randomized controlled trials to compare efficacy and safety outcomes among first-line IO treatment strategies versus standard platinum-based chemotherapy (CT) according to PD-L1 expression level (<1%, 1–49%, ≥50%). Pooled hazard ratios (HRs) and risk ratios (RRs) for progression-free survival (PFS), over…

A missense mutation associated to early onset breast cancer in a sicilian woman.

Involvement of non-coding RNAs in chemo- and radioresistance of colorectal cancer

Despite recent progress in understanding the cancer signaling pathways and in developing new therapeutic strategies, however, the resistance of colorectal cancer (CRC) cells to chemo- and radiotherapy represents the main hurdle to the successful treatment, leading to tumor recurrence and, consequently, a poor prognosis. Therefore, overcoming drug and radiation resistance, enhancing drug and radiation sensitivity of CRC cells, and improving the effi cacy of chemo- and radiotherapy have an important signifi cance in the treatment of CRC. The identifi cation of new molecular biomarkers which can predict therapy response and prognosis is one of the most signifi cant aims in pharmacogenomics and…

Gists eredo familiari e pediatrici: aspetti biomolecolari e clinici.

The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with wild-type or unknown EGFR status

// Giuseppe Bronte 1, * , Tindara Franchina 2, * , Massimiliano Alu 3, * , Giovanni Sortino 1 , Claudia Celesia 1 , Francesco Passiglia 1 , Giuseppina Savio 3 , Agata Laudani 3 , Alessandro Russo 2 , Antonio Picone 2 , Sergio Rizzo 1 , Michele De Tursi 4 , Elisabetta Gambale 4 , Viviana Bazan 1 , Clara Natoli 4 , Livio Blasi 3 , Vincenzo Adamo 2 , Antonio Russo 1 1 Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy 3 Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy 4 Department of Medical, Oral and Biotechnological …

What links BRAF to the heart function? new insights from the cardiotoxicity of BRAF inhibitors in cancer treatment

The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolonga…

Havep53 gene mutations and protein expression a different biological significance in colorectal cancer?

p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein over-expression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 prote…

Dietary restriction: could it be considered as speed bump on tumor progression road?

Dietary restrictions, including fasting (or long-term starvation), calorie restriction (CR), and short-term starvation (STS), are considered a strong rationale that may protect against various diseases, including age-related diseases and cancer. Among dietary approaches, STS, in which food is not consumed during designed fasting periods but is typically not restricted during designated feeding periods, seems to be more suitable, because other dietary regimens involving prolonged fasting periods could worsen the health conditions of cancer patients, being they already naturally prone to weight loss. Until now, the limited amount of available data does not point to a single gene, pathway, or …

Analysis of Germline Gene Copy Number Variants of Patients with Sporadic Pancreatic Adenocarcinoma Reveals Specific Variations

&lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; The rapid fatality of pancreatic cancer is, in large part, the result of diagnosis at an advanced stage in the majority of patients. Identification of individuals at risk of developing pancreatic adenocarcinoma would be useful to improve the prognosis of this disease. There is presently no biological or genetic indicator allowing the detection of patients at risk. Our main goal was to identify copy number variants (CNVs) common to all patients with sporadic pancreatic cancer. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We analyzed gene CNVs in leukocyte DNA from 31 patients with sporadic pancreatic adenocarcinoma and from 93 matched contr…

sj-docx-3-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-3-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Circular RNA in Exosomes

Circular RNAs (circRNAs) are a novel family of non-coding endogenous RNAs discovered in all eukaryotic cells and generated through a particular mechanism of alternative splicing called “back-splicing”. These molecules show multiple functions, by acting as modulators of gene and miRNA expression, and may have a role in several biological processes, such as cell proliferation and invasion with, tumour development and progression, and in several mechanisms underlying other diseases. Their presence has been shown to be abundant in several body fluids such as blood and saliva. Based on their biogenesis mechanism, cir- cRNAs may be categorized into five classes: exonic circRNAs, intronic circRNAs…

Aplotype analysis in four sicilian families with 5083del19bp-BRCA1.

POLE, POLD1, and NTHL1: the last but not the least hereditary cancer-predisposing genes

POLE, POLD1, and NTHL1 are involved in DNA replication and have recently been recognized as hereditary cancer-predisposing genes, because their alterations are associated with colorectal cancer and other tumors. POLE/POLD1-associated syndrome shows an autosomal dominant inheritance, whereas NTHL1-associated syndrome follows an autosomal recessive pattern. Although the prevalence of germline monoallelic POLE/POLD1 and biallelic NTHL1 pathogenic variants is low, they determine different phenotypes with a broad tumor spectrum overlapping that of other hereditary conditions like Lynch Syndrome or Familial Adenomatous Polyposis. Endometrial and breast cancers, and probably ovarian and brain tumo…

Nintedanib in NSCLC: evidence to date and place in therapy

The treatment of advanced non-small cell lung cancer (NSCLC) is currently driven by the detection of targetable oncogenic drivers, i.e. epidermal growth factor receptor, echinoderm microtubule-associated protein-like 4–anaplastic lymphoma kinase, etc. Those patients who are wildtype for known and valuable oncogenes can receive standard chemotherapy as first-line treatment, with the possibility of adding bevacizumab. With regard to second-line treatment, nintedanib can improve the efficacy of docetaxel. Nintedanib is a tyrosine kinase inhibitor targeting three angiogenesis-related transmembrane receptors. The usefulness of nintedanib as an anticancer agent for NSCLC has been proved by both …

Predictive Factors of Response to Sunitinib in Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs): A Multi-Institutional Study

Imatinib 400 mg is the standard of care for medical treatment of advanced GISTs. In the majority of cases, however, GISTs eventually develop resistance to imatinib. The optimal second line treatment has not been established yet and imatinib dose escalation (800 mg) or sunitinib represent two feasible options. The objective of this retrospective, multi-institutional, study is to analyze the validity of several parameters as possible predictive factors of response to sunitinib after imatinib failure. We reviewed 128 metastatic GISTs treated with sunitinib between January 2007 to June 2017. Primary tumour site, metastatic site, c-KIT/PDGFR-&amp;alpha; mutational status, PET-FDG status and type…

Can the tumor-agnostic evaluation of MSI/MMR status be the common denominator for the immunotherapy treatment of patients with several solid tumors?

Alterations in short-repetitive DNA sequences, known as microsatellite instability (MSI), can reflect deficiencies in Mismatch Repair (MMR) system which represents a major player in DNA integrity maintenance. The incidence of MSI-H/dMMR has been shown to be variable depending on the tumor type. Several studies confirmed that dMMR/MSI status, although less frequent than PD-L1 expression, may better predict response to immune-checkpoint inhibitors (ICIs) in patients with solid tumors. In October 2016, the FDA granted pembrolizumab as breakthrough therapy for the treatment of non-CRC, MSI-H/dMMR tumors, providing, for the first time, a tumor-agnostic indication. In the next future, the tissue-…

Nm-23-H1 expression does not predict clinical survival in colorectal cancer patients

The gene Nm23, which encodes for a nucleoside diphosphate kinase, has been defined as a metastasis-suppressor gene because of the inverse correlation between its expression and the metastatic capacity of the tumor cells. For colorectal cancer, however, the findings are equivocal. The aim of our study was to assess, in 160 patients undergoing surgery for colorectal cancer (CRC), the expression of the Nm23-H1 protein and to evaluate its possible associations with traditional clinicopathologic variables, with DNA-ploidy and proliferative activity (S-phase fraction, SPF), and with disease-free and overall survival of patients. Nm23-H1 expressions were evaluated on paraffin-embedded tissue by im…

Patterns of genomic instability in gastric cancer: clinical implications and perspectives

In gastric cancer (GC) the loss of genomic stability represents a key molecular step that occurs early in the carcinogenesis process and creates a permissive environment for the accumulation of genetic and epigenetic alterations in tumor suppressor genes and oncogenes. It is widely accepted that GC can follow at least two major genomic instability pathways, microsatellite instability (MSI) and chromosome instability (CIN). MSI is responsible for a well-defined subset of GCs. CIN represents a more common pathway comprising heterogeneous subsets of GC. In addition to MSI and CIN, the CpG islands methylator phenotype (CIMP) plays an important role in gastric carcinogenesis. CIMP may lead to th…

Prognostic vs predictive molecular biomarkers in colorectal cancer: is KRAS and BRAF wild type status required for anti-EGFR therapy?

An important molecular target for metastatic CRC treatment is the epidermal growth factor receptor (EGFR). Many potential biomarkers predictive of response to anti-EGFR monoclonal antibodies (cetuximab and panitumumab) have been retrospectively evaluated, including EGFR activation markers and EGFR ligands activation markers. With regard to the "negative predictive factors" responsible for primary or intrinsic resistance to anti-EGFR antibodies a lot of data are now available. Among these, KRAS mutations have emerged as a major predictor of resistance to panitumumab or cetuximab in the clinical setting and several studies of patients receiving first and subsequent lines of treatment have sho…

sj-docx-10-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-10-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

sj-docx-11-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-11-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Effects of anti-miR-182 on TSP-1 expression in human colon cancer cells: there is a sense in antisense?

Abstract: Objective: miRNAs are attractive molecules for cancer treatment, including colon rectal cancer (CRC). We investigate on the molecular mechanism by which miR-182 could regulate thrombospondin-1 (TSP-1) expression, a protein down-regulated in CRC and inversely correlated with tumor vascularity and metastasis. Background: MicroRNAs are small non-coding RNAs that regulate the expression of different genes, involved in cancer progression, angiogenesis and metastasis. miR-182, over-expressed in colorectal cancer (CRC), has like predictive target thrombospondin-1 (TSP-1), a protein inversely correlated with tumor vascularity and metastasis that results downregulated in different types of…

TP53 in exon 5 and s-Phase fraction but not mutations in Ras gen family and DNA-ploidy are indipendent indicators in laryngeal squamous cell carcinoma

sj-docx-6-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-6-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Challenges and advances for the treatment of renal cancer patients with brain metastases: From immunological background to upcoming clinical evidence on immune-checkpoint inhibitors

The introduction of checkpoint inhibitors (ICIs) in renal cell carcinoma (RCC) treatment landscape, resulted in improvements in overall survival (OS) in metastatic patients. Brain metastases (BMs) are a specific metastatic site of interest representing a predictive factor of poor prognosis. Patients with BMs were usually excluded from prospective clinical trials in the past. Despite recent evidence suggest the efficacy and safety of ICIs, the BMs treatment remains a challenge; the immunotherapy responsiveness seems to be multifactorial and dependent on several factors, such as the genetic intratumor heterogeneity and the immunosuppressive role of the brain tumor microenvironment. This revie…

Farletuzumab for NSCLC: Exploiting a well-known metabolic pathway for a new therapeutic strategy

Abstract: Introduction: The therapeutic options for NSCLC are limited barring targeted drugs, such as EGFR tyrosine-kinase inhibitors and anaplastic lymphoma kinase inhibitors, for patients bearing oncogenic mutations. Platinum-based chemotherapy remains the best strategy for most patients. New targeted drugs, including mAbs and small molecules, are currently under clinical investigation for treating NSCLC patients. Areas covered: The authors of this article focus on farletuzumab, a mAb targeting folate receptor, which has been studied in ovarian cancer and various other malignancies. In this review, the authors review its potential as therapy for NSCLC, because of the biological rationale …

An update on the conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting TKI-based therapy.

Introduction: The angiogenesis mechanism is considered a crucial point in neoplastic development. A growing number of multi-targeted tyrosine kinase inhibitors (TKI) has been developed and approved for cancer treatment during the last few years. Cardiac side effects still remain an issue to manage nowadays. These drugs mechanisms and toxicities have already been discussed, hence the authors will report updates on these already available drugs. Area covered: This manuscript provides an updated review on the new mechanisms involved in angiogenesis and cardiotoxicity that are TKI-related. Here is reported an overview of the already available and the most recent TKIs under investigation in the …

1535P Exploring the dynamic crosstalk between immune system and genetics in a cohort of 116 completely resected gastrointestinal stromal tumors (GISTs)

162P Prevalence and spectrum analysis of germline BRCA1 and BRCA2 variants of unclear significance in HBOC Syndrome: Decoding the mysterious signals of the genome

sj-docx-7-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-7-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

EGFR inhibition in NSCLC: New findings…. and opened questions?

The targeted inhibition of epidermal growth factor receptor (EGFR) has represented a milestone in the treatment of lung cancer. Several studies convincingly and consistently demonstrated a significant superiority of EGFR-TKIs over standard platinum-chemotherapy in EGFR-mutated NSCLC patients, leading to the sequential approval of gefitinib, erlotinib and afatinib as new standard first-line clinical treatment. To date we are witnessing a second revolution in the management of EGFR-positive NSCLC thanks to the development of new treatment strategies aiming to overcome acquired resistance to TKIs and ultimately improve patients’ outcomes. In this review we summarize the most important recent f…

P07.02 Detection of Molecular Residual Disease (MRD) using ctDNA in NSCLC: A Systematic Review and Meta-Analysis

Clinical Potential of Circulating Cell-Free DNA (cfDNA) for Longitudinally Monitoring Clinical Outcomes in the First-Line Setting of Non-Small-Cell Lung Cancer (NSCLC): A Real-World Prospective Study

Background: Despite the increasing implementation of targeted and immunotherapy-based treatments, the prognosis of patients with advanced NSCLC remains dismal. We prospectively evaluated longitudinal plasma cfDNA kinetics as an early marker of therapeutic efficacy in patients with advanced NSCLC undergoing standard first-line treatments. Methods: From February 2020 to May 2022, treatment-na&iuml;ve patients with advanced NSCLC were consecutively enrolled at the Medical Oncology Unit of the Paolo Giaccone University Hospital, Palermo (Italy). We quantified cfDNA in terms of ng/&mu;L using a QubitTM dsDNA HS Assay Kit. The agreement between the cfDNA and radiologic response was evaluated from…

Impact of microRNAs in Resistance to Chemotherapy and Novel Targeted Agents in Non-Small Cell Lung Cancer

Despite recent advances in understanding the cancer signaling pathways and in developing new therapeutic strategies, non-small cell lung cancer (NSCLC) shows grim prognosis and high incidence of recurrence. Insufficient dis- ruption of oncogenic signaling and drug resistance are the most common causes of tumor recurrence. Drug resistance, in- trinsic or acquired, represents a main obstacle in NSCLC therapeutics by limiting the efficacy both of conventional che- motherapeutic compounds and new targeted agents. Therefore, novel and more innovative approaches are required for treatment of this tumor. MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression by sequ…

Absence of germline CDKN2A mutation in Sicilian Patients with Familial Malignant Melanoma: could it be a population-specific genetic signature?

Germline CDKN2A mutations have been described in 25% to 40% of melanoma families from several countries. Sicilian population is genetically different from the people of Europe and Northern Italy because of its historical background, therefore familial melanoma could be due to genes different from high-penetrance CDKN2A gene. Four hundred patients with cutaneous melanoma were observed in a 6-years period at the Plastic Surgery Unit of the University of Palermo. Forty-eight patients have met the criteria of the Italian Society of Human Genetics (SIGU) for the diagnosis of familial melanoma and were screened for CDKN2A and CDK4 mutations. Mutation testing revealed that none of the families car…

Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…

Not all KIT 557/558 codons mutations have the same prognostic influence on recurrence-free survival: breaking the exon 11 mutations in gastrointestinal stromal tumors (GISTs)

Background: Although the gastrointestinal stromal tumor (GIST) genotype is not currently included in risk-stratification systems, a growing body of evidence shows that the pathogenic variant (PV) type and codon location hold a strong prognostic influence on recurrence-free survival (RFS). This information has particular relevance in the adjuvant setting, where an accurate prognostication could help to better identify high-risk tumors and guide clinical decision-making. Materials and Methods: Between January 2005 and December 2020, 96 patients with completely resected GISTs harboring a KIT proto-oncogene receptor tyrosine kinase ( KIT) exon 11 PV were included in the study. We analyzed the t…

Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumours (mGISTs)

Abstract Background Gastrointestinal stromal tumours (GISTs) account for 1% of all primary gastrointestinal cancers. In cancer, suppressive immune checkpoints, including butyrophilin sub-family 3A/CD277 receptors (BTN3A), programmed death protein (PD-1) and its ligand PD-L1, are often hyper-activated to ensure an effective evasion of tumor cells from immune surveillance. Since recent studies showed that PD-1 and PD-L1 expression in cancer may be an important prognostic factor, the aim of our study was to investigate if soluble forms of inhibitory immune checkpoints can help predict survival in metastatic GIST patients. Methods Using specific homemade ELISA assays not yet commercially availa…

P48.10 Chemo-Immunotherapy in the Frontline of Extensive-Stage Small Cell Lung Cancer: A Systematic Review and Indirect Comparisons

sj-docx-4-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-4-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

I tumori della mammella e/o dell’ovaio di tipo eredofamiliare: strategie di prevenzione nelle donne ad alto rischio

Numerosi fattori sono stati coinvolti nell’insorgenza del carcinoma mammario e dell’ovaio tra cui l’età, fattori ormonali e riproduttivi come l’età e il numero di gravidanze e l’utilizzo di contraccettivi orali e, in minor misura, fattori ambientali e stili di vita. Le possibilità per la gestione clinica delle pazienti considerate ad alto rischio di sviluppare carcinoma della mammella e/o dell’ovaio includono chirurgia profilattica (es. mastectomia bilaterale profilattica o ovarosalpingectomia bilaterale), chemioprevenzione (principalmente tamoxifene e raloxifene ma anche, più recentemente, inibitori dell’aromatasi nelle donne ad alto rischio in postmenopausa), cambiamenti nelle abitudini d…

Monoclonal antibodies for the treatment of non-haematological tumours: update of an expanding scenario.

Abstract: Introduction: The identification of cell membrane-bound molecules with a relevant role in cancer cell survival prompted the development of moAbs to block the related pathways. In the last few years, the number of approved moAbs for cancer treatment has constantly increased. Many of these drugs significantly improved the survival outcomes in patients with solid tumours. Areas covered: In this review, all the FDA-approved moAbs in solid tumours have been described. This is an update of moAbs available for cancer treatment nowadays in comparison with the moAbs approved until few years ago. The moAbs under development are also discussed here. Expert opinion: The research on cancer ant…

Effects of PPARγ agonists on the expression of leptin and vascular endothelial growth factor in breast cancer cells.

The obesity hormone leptin has been implicated in breast cancer development. Breast cancer cells express the leptin receptor and are able to synthesize leptin in response to obesity-related stimuli. Furthermore, leptin is a positive regulator of vascular endothelial growth factor (VEGF) and high levels of both proteins are associated with worse prognosis in breast cancer patients. Peroxisome proliferator-activated receptor γ (PPARγ) ligands are therapeutic agents used in patient with Type 2 diabetes and obesity which have recently been studied for their potential anti-tumor effect. Here, we studied if these compounds, ciglitazone and GW1929, can affect the expression of leptin and VEGF in b…

La consulenza genetica in oncologia: implicazioni biomolecolari e cliniche.

sj-docx-9-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-9-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Impact of deleterious variants in other genes beyond BRCA1/2 detected in breast/ovarian and pancreatic cancer patients by NGS-based multi-gene panel testing: looking over the hedge

Background Hereditary breast cancer (BC), ovarian cancer (OC), and pancreatic cancer (PC) are the major BRCA-associated tumours. However, some BRCA1/2-wild-type (wt) patients with a strong personal and/or family history of cancer need a further genetic testing through a multi-gene panel containing other high- and moderate-risk susceptibility genes. Patients and methods Our study was aimed to assess if some BC, OC, or PC patients should be offered multi-gene panel testing, based on well-defined criteria concerning their personal and/or family history of cancer, such as earliness of cancer onset, occurrence of multiple tumours, or presence of at least two or more affected first-degree relativ…

Detection and clinical relevance of free-circulating tumor DNA in blood of patients with colorectal cancer

Patterns of K-ras mutation in colorectal carcinomas from Iran and Italy (a Gruppo Oncologico dell'Italia Meridionale study): influence of microsatellite instability status and country of origin

Background: K-ras mutations are a key step in colorectal cancer progression. Such mutations have been widely studied in case series from Western countries but there are few data on the rate and spectrum of mutations in tumors from countries where the epidemiological features of the disease are different. Patients and methods: Tumor samples from 182 Iranian colorectal cancer patients (170 sporadic cases and 12 HNPCC cases) were screened for K-ras mutations at codons 12, 13 and 61 by sequencing analysis. The cases were also characterized for microsatellite instability at mononucleotide repeats by PCR and fragment analysis, and classified according to microsatellite instability status. The fre…

Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis

Background: Tissue evaluation for RAS (KRAS or NRAS) gene status in metastatic colorectal cancer (mCRC) patients represent the standard of care to establish the optimal therapeutic strategy. Unfortunately, tissue biopsy is hampered by several critical limitations due to its invasiveness, difficulty to access to disease site, patient’s compliance and, more recently, neoplastic tissue spatial and temporal heterogeneity. Methods: The authors performed a systematic literature review to identify available trials with paired matched tissue and ctDNA RAS gene status evaluation. The authors searched EMBASE, MEDLINE, Cochrane, www.ClinicalTrials.gov , and abstracts from international meetings. In to…

Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay

Individual response to immune checkpoint inhibitors (ICIs) is currently unpredictable in patients with melanoma. Recent findings highlight a striking improvement in the clinical outcomes of overweight/obese patients treated with ICIs, which seems driven, at least in part, by programmed cell death protein 1 (PD-1)-mediated T-cell dysfunction. A putative role of butyrophilins (BTNs) is under investigation as a novel mechanism of cancer immune evasion and obesity-associated inflammation. This study investigates the role of baseline plasma levels of soluble PD-1 (sPD-1), soluble programmed cell death ligand 1 (sPD-L1), BTN2A1 (sBTN2A1), BTN3A1 (sBTN3A1), along with body mass index (BMI), as pr…

The role of microRNAs in driving EGFR-TKI resistance in NSCLC cell lines

Background: the inhibition of EGFR kinase activity by tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, can result in improved response and prolonged progression-free survival (PFS) in NSCLC patients harboring sensitizing exon 19del and exon 21 L858R mutations. Unfortunately, almost all patients will develop resistance to EGFR-TKI, in particular T790M is the most frequent mutation. Nowadays, new methods are urgently needed for a rapid, cost-effective and non-invasive identification of biomarkers as a valuable tool for obtaining the genetic follow-up data during the course of the disease. Circulating microRNAs might represent a new precious biomarker for patients’ moni…

The prognostic role of KRAS and BRAF in patients undergoing surgical resection of colorectal cancer liver metastasis: a systematic review and meta-analysis

Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of liver metastasis (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Materials and Methods: Data from all published studies reporting survival outcomes (RFS and/or OS) of CRC patients who received resection of CLM, stratified by KRAS and/or BRAF mutation status were collected by sear…

sj-docx-8-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-8-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Combination of eribulin (E) and capecitabine (C) in elderly metastatic breast cancer (MBC): Update of a new option suitable in older elderly.

9540 Background: E mesylate, a nontaxane microtubule dynamics inhibitor is widely prescribed for MBC pts pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&...

The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Background: The circulating tumor DNA (ctDNA) diagnostic accuracy for detecting phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha ( PIK3CA) mutations in breast cancer (BC) is under discussion. We aimed to compare plasma and tissue PIK3CA alterations, encompassing factors that could affect the results. Methods: Two reviewers selected studies from different databases until December 2020. We considered BC patients with matched tumor tissue and plasma ctDNA. We performed meta-regression and subgroup analyses to explore sources of heterogeneity concerning tumor burden, diagnostic technique, sample size, sampling time, biological subtype, and hotspot mutation. Pooled sensitiv…

“Back to a false normality”: new intriguing mechanisms of resistance to PARP inhibitors

Several evidences have shown that BRCA mutations increased tumor-cells sensitivity to PARP inhibitors by synthetic lethality leading to an accelerated development of several compounds targeting the PARP enzymes system as anticancer agents for clinical setting. Most of such compounds have been investigated in ovarian and breast cancer, showing promising efficacy in BRCA-mutated patients. Recently clinical studies of PARP-inhibitors have been extended across different tumor types harboring BRCA-mutations, including also "BRCA-like" sporadic tumors with homologous recombination deficiency (HRD). This review summarizes the biological background underlying PARP-inhibition, reporting the results …

Type and gene location of kit mutations predict progression-free survival to first-line imatinib in gastrointestinal stromal tumors: A look into the exon

In previous studies on localized GISTs, KIT exon 11 deletions and mutations involving codons 557/558 showed an adverse prognostic influence on recurrence-free survival. In the metastatic setting, there are limited data on how mutation type and codon location might contribute to progression-free survival (PFS) variability to first-line imatinib treatment. We analyzed the type and gene location of KIT and PDGFRA mutations for 206 patients from a GIST System database prospectively collected at an Italian reference center between January 2005 and September 2020. By describing the mutational landscape, we focused on clinicopathological characteristics according to the critical mutations and inve…

Carcinoma ereditario dell'ovaio (Ereditary Ovarian Cancer)

sj-docx-2-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-2-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

DNA aneuploidy and high proliferative activity but not K-ras-2 mutations as independent predictors of clinical outcome in operable gastric carcinoma: Results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study

BACKGROUND The prognostic value of DNA ploidy, S-phase fraction (SPF) and K-ras-2 mutations in gastric carcinoma (GC) has not yet been clearly defined. The aim of this study was to clarify the association between biomolecular variables, tumor characteristics, and clinical outcome in GC patients. METHODS Resected specimens from a consecutive series of 69 patients with GC who underwent potentially curative surgery were studied prospectively. DNA ploidy and SPF were assessed by flow cytometry on multiple frozen tumor samples, whereas K-ras-2 mutations were detected by polymerase chain reaction followed by single-strand conformation polymorphism. All the patients involved in this study were fol…

the proximal leptin gene promoter is regulated by ppar gamma agonist in MCF-7 and MDA-MB-231 breast cancer cells

BRCA1 germline mutations in Sicilian breast and/or ovarian cancer families and their implications for genetic counselling.

Safety of high doses of somatostatin analogs in well differentiated NENs in elderly

Abstract Background Neuroendocrine neoplasms (NENs) are a group of heterogeneous neoplasms which can be treated with different therapies: in well differentiated (WD) NENs analogs of somatostatin (SSA) can be used considering their proved antineoplastic and antisecretory effects. This is a multicenter study to investigate the safety of high doses (HDD) analogs of somatostatin (SSA) in WD NENs with particular attention for patients over 70 years of age. Methods We collected clinical data from 13 Italian NENs dedicated Units. Patients with WD NENs, in progression on previous treatments, included SSA, and subsequently treated with HDD-SSA, were considered. Results 170 pts were included: 61.76% …

TP53 mutations are not prognostic independent indicators in bladder cancer.

VUS variants in BRCA genes of hereditary breast/ovarian cancer

Pleomorphic adenoma and adenoid-cystic carcinoma of salivary glands: immunohistochemical assessment of proliferative activity in comparison with flow-cytometric study

In this study, 32 pleomorphic adenomas (PAs) and seven adenoid cystic carcinomas (ACCs) were analysed for the evaluation of proliferating cell nuclear antigen (PCNA) indices and flow cytometric variables. Our aim was to assess any possible relationship between these parameters and the clinico-pathological variables and to clarify their histogenesis and reasons for their biological differences. The tumours were divided into three groups, mainly epithelial (E), myxoid (M) and chondroid (C); PCNA labelling index (LI) and weighted mean index (WI) and the WI/LI ratio were analysed in the predominant components; a single PCNA index, weighted by the percentage of each component, was also calculate…

sj-pdf-1-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-1-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Detection and quantification of mammaglobin in the blood of breast cancer patients: can it be useful as a potential clinical marker? Preliminary results of a GOIM (Gruppo Oncologico dell'Italia Meridionale) prospective study.

BACKGROUND: Mammaglobin is expressed mainly in mammary tissue, overexpressed in breast cancer (BC) and rarely in other tissue. The aim of this study was to assess the sensitivity and specificity of transcript MGB1 detection and to evaluate the role of MGB1 as potential clinical marker for the detection of disseminated cancer cells in the blood of BC patients. PATIENTS AND METHODS: A consecutive series of 23 BC tissues, 36 peripheral blood BC samples and 35 healthy peripheral blood samples was prospectively recruited to investigate MGB1 expression by means of a quantitative Real Time RT-PCR assay. RESULTS: MGB1 overexpression in tissue samples of BC patients is significantly associated only …

Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

Highlights • Hormonal receptors positive breast tumor and prostate cancer are managed with endocrine therapies. • Endocrine therapies designed for breast and prostate cancer are often associated to serious adverse skeletal related events, such fractures. • Denosumab is a monoclonal anti-body binding RANKL which acts as inhibitor of osteoclasts activity, thus increasing bone mass. • Denosumab was showed to strongly prevent hormonal therapies-related skeletal issues. • Denosumab administration results safe in bone mass increase and reduction of fractures risk.

Stabilizing versus Destabilizing the Microtubules: A Double-Edge Sword for an Effective Cancer Treatment Option?

Microtubules are dynamic and structural cellular components involved in several cell functions, including cell shape, motility, and intracellular trafficking. In proliferating cells, they are essential components in the division process through the formation of the mitotic spindle. As a result of these functions, tubulin and microtubules are targets for anticancer agents. Microtubule-targeting agents can be divided into two groups: microtubule-stabilizing, and microtubule-destabilizing agents. The former bind to the tubulin polymer and stabilize microtubules, while the latter bind to the tubulin dimers and destabilize microtubules. Alteration of tubulin-microtubule equilibrium determines th…

Tumor Board and Molecular Tumor Board

Specialized expertise and cooperation between different professional figures are increasingly needed for the management of cancer patients. Tumor boards (TB) can address this issue by gathering together different healthcare providers to periodically discuss challenging cases.

sj-pdf-1-tam-10.1177_1758835920975326 – Supplemental material for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Supplemental material, sj-pdf-1-tam-10.1177_1758835920975326 for BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients by Lorena Incorvaia, Daniele Fanale, Marco Bono, Valentina Calò, Alessia Fiorino, Chiara Brando, Lidia Rita Corsini, Sofia Cutaia, Daniela Cancelliere, Alessia Pivetti, Clarissa Filorizzo, Maria La Mantia, Nadia Barraco, Stefania Cusenza, Giuseppe Badalamenti, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

sj-docx-13-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-13-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

How do skeletal morbidity rate and special toxicities affect 12-week versus 4-week schedule zoledronic acid efficacy? A systematic review and a meta-analysis of randomized trials

Abstract Background Zoledronic Acid is a bisphosphonate used in a 4-week schedule for the treatment of bone metastases. Some randomized trials supported its role also when administered every 12 weeks. Methods we performed a systematic review and a meta-analysis in order to evaluate the two different schedules in terms of skeletal morbidity rate (SMR), skeletal related events (SRE) and adverse events (AEs). Results our results showed a clinical difference favouring the 12-week schedule in terms of AEs (RR 1.17, 95% CI 1.06–1.29). No signifcant differences were found for SMR (RR 0.97, 95% CI 0.84–1.13) and SRE (RR 1.02, 95% CI 0.89–1.16). Conclusions Our findings support in clinical practice …

sj-docx-5-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-5-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Germline copy number variation in theYTHDC2gene: does it have a role in finding a novel potential molecular target involved in pancreatic adenocarcinoma susceptibility?

Abstract: Objective: The vast majority of pancreatic cancers occurs sporadically. The discovery of frequent variations in germline gene copy number can significantly influence the expression levels of genes that predispose to pancreatic adenocarcinoma. We prospectively investigated whether patients with sporadic pancreatic adenocarcinoma share specific gene copy number variations (CNVs) in their germline DNA. Patients and methods: DNA samples were analyzed from peripheral leukocytes from 72 patients with a diagnosis of sporadic pancreatic adenocarcinoma and from 60 controls using Affymetrix 500K array set. Multiplex ligation-dependent probe amplification (MLPA) assay was performed using a s…

Ras family genes: An interesting link between cell cycle and cancer

Ras genes are evolutionary conserved and codify for a monomeric G protein binding GTP (active form) or GDP (inactive form). The ras genes are ubiquitously expressed although mRNA analysis suggests different level expression in tissue. Mutations in each ras gene frequently were found in different tumors, suggesting their involvement in the development of specific neoplasia. These mutations lead to a constitutive active and potentially oncogenic protein that could cause a deregulation of cell cycle. Ras protein moderates cellular responses at several mitogens and/or differentiation factors and at external stimuli. These stimuli activate a series of signal transduction pathways that either can…

Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients

Background: We investigated whether early dynamic changes of circulating free (cfDNA) levels as well as the neutrophil to lymphocyte ratio (NLR) could predict nivolumab effectiveness in pretreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were enrolled. Patients underwent a computed tomography scan and responses were evaluated by the response evaluation criteria in solid tumors. Peripheral blood samples were obtained from the patients and the cfDNA level as well as the NLR were assessed. Time to progression (TTP) and overall survival (OS) were determined. Results: Patients with increased cfDNA &gt;20%…

166P Hereditary breast, ovarian and pancreatic cancers: Looking beyond the BRCA1/2 genes

The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M mutation in NSCLC: a systematic review and meta-analysis

AbstractThis pooled analysis aims at evaluating the diagnostic accuracy of circulating tumor (ct) DNA for the detection of EGFR-T790M mutation in NSCLC patients who progressed after EGFR-TKIs. Data from all published studies, reporting both sensitivity and specificity of plasma-based EGFR-T790M mutation testing by ctDNA were collected by searching in PubMed, Cochrane Library, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference of Lung Cancer meeting proceedings. A total of twenty-one studies, with 1639 patients, were eligible. The pooled sensitivity of ctDNA analysis was 0.67 (95% CI: 0.64–0.70) and the pooled specificity was 0.80 (95% CI: 0.77–0…

Detection of Germline Mutations in a Cohort of 139 Patients with Bilateral Breast Cancer by Multi-Gene Panel Testing: Impact of Pathogenic Variants in Other Genes beyond BRCA1/2

Simple Summary Many bilateral breast cancer patients with increased hereditary susceptibility to breast cancer result negative for BRCA1 or BRCA2 pathogenic variants and, thus, need a further genetic testing through a broader gene panel. Some patients with negative test result for BRCA1/2 pathogenic variants may harbor pathogenic variants in other breast cancer susceptibility genes, including ATM, CHEK2, PALB2, PTEN, TP53. Of course, the use of a multi-gene panel provides clinicians more information through a single test. Therefore, we focused on potential clinical impact of a NGS-based multi-gene panel testing in bilateral breast cancer patients, in order to evaluate the utility of perform…

STAT proteins: From normal control of cellular events to tumorigenesis

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that participate in normal cellular events, such as differentiation, proliferation, cell survival, apoptosis, and angiogenesis following cytokine, growth factor, and hormone signaling. STATs are activated by tyrosine phosphorylation, which is normally a transient and tightly regulates process. Nevertheless, several constitutively activated STATs have been observed in a wide number of human cancer cell lines and primary tumors, including blood malignancies and solid neoplasias. STATs can be divided into two groups according to their specific functions. One is …

A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and a…

The Long and Winding Road to Useful Predictive Factors for Anti-EGFR Therapy in Metastatic Colorectal Carcinoma: The KRAS/BRAF Pathway

Monoclonal antibodies targeting the epidermal growth factor receptor (EGFR) have improved outcomes for patients with metastatic colorectal carcinoma. Among patients not carrying activating mutations in the KRAS gene, only a limited number will experience tumor response to these therapeutic agents. The role of BRAF mutations in determining resistance to this treatment is emerging through preclinical and clinical studies. Standardization and validation of laboratory mutation analysis is needed to allow an optimal use of anti-EGFR therapies in the management of colorectal carcinoma. Clinical single-arm and randomized studies were conducted both in first-line and refractory settings to evaluate…

Effects of erybuline/capecitabine (EC) treatment in very elderly women (VEW) with MBC.

e12508 Background: Eribuline mesylate, is widely prescribed for MBC pts alone or in combination with Capecitabine in patients pretreated with at least 1-2 lines of chemotherapy, including anthracyclines and taxanes (A&amp;T). Elderly Patients (EP) develop rapid and sometimes fatal toxicity during treatments due to pharmacokinetic features of these drugs.A combination schedule (E+C) to evaluate its suitability for VEW with MBC patients ,was used in this study. Methods: Treatment plan: E 0.96 mg/sqm IV on d1 every 21d - C 900 mg/sqm bid d1-14 every 28d (Dose-adjustement if necessary was according to Kintzel-Dorr’s formula for elderly), schedule administration continued until progression or i…

Potential miRNAs involved in molecular pathways mediating the anticancer effects of short term starvation in breast cancer cells treated with doxorubicin

Background: In recent years, increasing evidences showed that several types of dietary approaches restricting food intake, including Short Term Starvation (STS), may exert a protective role against aging and other age-related pathologies as well as cancer. Interestingly, the dietary restriction showed significant anticancer effects able to prevent cancer onset, slow its progression and improve therapy response. Since recent studies showed that miRNAs may modulate sensibility/resistance to antiblastic therapy, the aim of our study was to investigate the STS-induced molecular changes in breast cancer cells treated with doxorubicin, focusing our attention on miRNA expression profile. Materials…

sj-pdf-4-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-4-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

247P Population-based testing for hereditary breast and ovarian cancer in a cohort of 1,346 patients from Southern Italy (Sicily): When historical background affects genetics

2020 Reply to: Denosumab for bone health in prostate and breast cancer patients receiving endocrine therapy? A systematic review and a meta-analysis of randomized trials

sj-docx-6-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-6-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

TP53 and p16INK4A, but not H-KI-Ras, are involved in tumorigenesis and progression of pleomorphic adenomas.

The putative role of TP53 and p16INK4A tumor suppressor genes and Ras oncogenes in the development and progression of salivary gland neoplasias was studied in 28 cases of pleomorphic adenomas (PA), 4 cases of cystic adenocarcinomas, and 1 case of carcinoma ex-PA. Genetic and epigenetic alterations in the above genes were analyzed by Polymerase Chain Reaction/Single Strand Conformational Polymorphism (PCR/SSCP) and sequencing and by Methylation Specific-PCR (MS-PCR). Mutations in TP53 were found in 14% (4/28) of PAs and in 60% (3/5) of carcinomas. Mutations in H-Ras and K-Ras were identified in4%(1/28) and7% (2/28) of PAs, respectively. Only 20% (1/5) of carcinomas screened displayed mutatio…

BRCA1/BRCA2 genes mutational screening in Sicilian breast and/or ovarian cancer families.

The role of microRNAs in cancer: diagnostic and prognostic biomarkers and targets of therapies

Introduction: miRNAs are noncoding RNAs that target specific mRNA with subsequent regulation of particular genes, implicated in various biological processes. In cancer, miRNAs could show a different expression from normal tissues. miRNAs have a role as oncogenes when they target tumor suppressor genes and similarly they are tumor suppressors when they target oncogenes. Areas covered: In this review, areas covered include the role of miRNAs in cancer diagnosis, prognosis and research for achievement of therapeutic strategies implicating miRNAs in oncology. As biogenesis of miRNAs is fundamental to understand their usefulness, this has also been discussed. Both miRNA expression profiles in ca…

Breast Cancer in Men: Oncology

Breast cancer in men (BCiM) is a very rare disease that is still understudied and most of the published data comes from small cohorts of patients, compared to breast cancer in women. Genetic factors are among the most clearly established risk factors for male breast cancer, and mainly involve BRCA1 and BRCA2 tumor-suppressor genes.

Can KRAS and BRAF mutations limit the benefit of liver resection in metastatic colorectal cancer patients? A systematic review and meta-analysis.

Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metastases (CLM), showing conflicting results. This meta-analysis aims to review all the studies reporting survival outcomes (recurrence free survival (RFS), and/or overall survival (OS)) of patients undergoing resection of CLM, stratified according to KRAS and/or BRAF mutation status. Background: Clinical trials investigated the potential role of both KRAS and BRAF mutations, as prognostic biomarkers, in colorectal cancer (CRC) patients who underwent surgical treatment of CRC-related liver metast…

The resistance related to targeted therapy in malignant pleural mesothelioma: Why has not the target been hit yet?

Abstract: Malignant pleural mesothelioma (MPM) is an aggressive tumor of the pleura with a poor prognosis. The most active first-line regimens are platinum compounds and pemetrexed. There is no standard second-line treatment in MPM. Advances in the understanding of tumor molecular biology have led to the development of several targeted treatments, which have been evaluated in clinical trials. Unfortunately none of the explored targeted treatments can currently be recommended as routine treatment in MPM. We reviewed the biological pathways involved in MPM, the clinical trials about targeted therapy, and possible related mechanisms of resistance. We suggest that specific genetic markers are n…

TP 53, H-K-Ras, P16INK4A gene molecular analysis in salivary gland tumors.

Search_strategy_-_Supplemental_Material_1_final – Supplemental material for Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis

Supplemental material, Search_strategy_-_Supplemental_Material_1_final for Detection of RAS mutations in circulating tumor DNA: a new weapon in an old war against colorectal cancer. A systematic review of literature and meta-analysis by Antonio Galvano, Simona Taverna, Giuseppe Badalamenti, Lorena Incorvaia, Marta Castiglia, Nadia Barraco, Francesco Passiglia, Fabio Fulfaro, Giordano Beretta, Giovanni Duro, Bruno Vincenzi, Pierosandro Tagliaferri, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Hereditary breast and ovarian cancer in families from southern Italy (Sicily)—Prevalence and geographic distribution of pathogenic variants in BRCA1/2 genes

Recent advances in the detection of germline pathogenic variants (PVs) in BRCA1/2 genes have allowed a deeper understanding of the BRCA-related cancer risk. Several studies showed a significant heterogeneity in the prevalence of PVs across different populations. Because little is known about this in the Sicilian population, our study was aimed at investigating the prevalence and geographic distribution of inherited BRCA1/2 PVs in families from this specific geographical area of Southern Italy. We retrospectively collected and analyzed all clinical information of 1346 hereditary breast and/or ovarian cancer patients genetically tested for germline BRCA1/2 PVs at University Hospital Policlini…

1818P Body mass index (BMI) is not a cancer risk factor for BRCA1/2 carriers: A systematic review and meta-analysis of case-control studies

Detection and clinical relevance of free circulating tumor DNA in blood of patients with gastrointestinal cancer

The molecular changes driving the carcinogenesis in Barrett's esophagus: which came first, the chicken or the egg?

Esophageal adenocarcinoma originates from columnar metaplastic epithelium of the distal esophagus. Various steps for this carcinogenetic process are known. Before the onset of high-grade dysplasia and adenocarcinoma, endoscopic surveillance is possible. However, because of the high cost of long-term surveillance, predictive factors for cancer are being evaluated to identify subjects with metaplasia who have a higher risk of developing malignancy. Molecular changes seem suitable for this purpose, but could require a high resource expenditure. While trying to identify the best predictive factors for cancer risk, molecular changes and differences in miRNA expression profile between the various…

Genotype analysis of colorectal carcinomas through laser pressare catapulting (LPC)

Recently, new chemotherapy agents which target the non-structural components of mitosis have been developed. An important protein involved in several mitotic phases is the Aurora-A protein. By means of the phosphorylation of different substrates, Aurora-A regulates the correct development of the various phases of mitosis. The kinase activity of this protein makes Aurora-A an excellent candidate as an oncogene. The first data of Aurora-A involvement in cancer regarded the identification of Aurora-A overexpression in primary breast and colon tumour samples. With regard to the predictive role of Aurora-A, it has been shown that its overexpression disrupts the spindle checkpoint activated by pa…

TP53, H-K-RAS, P16INK4A GENE MOLECULAR ANALYSIS IN SALIVARY GLAND TUMORS

sj-docx-13-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-13-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC).

Recently, immunotherapy has been shown to be an effective and helpful therapeutic option for the treatment of advanced non-small-cell lung cancer (NSCLC). The activity of antitumor T cells may be restored through the checkpoint blockade using anti-programmed death 1 or anti-programmed death ligand 1 (PD-L1) antibodies, showing, in several cancer patients, an increased progression-free survival and overall survival compared with classical chemotherapy. As recently shown by several studies, the PD-L1 expression levels in tumors may offer a selection criterion for patients to predict their immunotherapy response. In particular, NSCLC patients with high tumor PD-L1 levels (proportional score ≥ …

Monoclonal antibodies and antibody fragments: state of the art and future perspectives in the treatment of non-haematological tumors

Introduction: The use of monoclonal antibodies is one of the strategies for targeting the specific key points of the main pathways of cancer growth and survival, but only a few antibodies have offered a clear clinical benefit in the treatment of non-haematological malignancies. Areas covered: This review summarizes the general properties of monoclonal antibodies, including structure, nomenclature and production techniques. The antibodies approved for use in clinical practice for the treatment of non-haematological tumors and those antibodies still being developed in this setting are briefly described. The types of antibody fragments are also reported. Expert opinion: Monoclonal antibodies w…

sj-pdf-2-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-2-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Cardiovascular Damage in Clinical Trials

The Cardio-oncology field has grown considerably in the last two decades. The remarkable increase in the number of molecules used in oncology has brought with it a huge set of cardiovascular adverse events. For this reason, it is necessary to intervene on the early stages of drug development. This is what the Food and Drug Administration aims to do. This purpose can be achieved through a more careful analysis of the adverse event, development of guidelines, and identification of objective parameters that could guide the researcher in defining precisely the adverse event. It is also necessary to use additional methods not yet used in clinical trials that can allow an early detection of adver…

Baseline plasma levels of soluble PD-1, PD-L1, and BTN3A1 predict response to nivolumab treatment in patients with metastatic renal cell carcinoma: a step toward a biomarker for therapeutic decisions

Despite a proportion of renal cancer patients can experiment marked and durable responses to immune-checkpoint inhibitors, the treatment efficacy is widely variable and identifying the patient who will benefit from immunotherapy remains an issue. We performed a prospective study to investigate if soluble forms of the immune-checkpoints PD-1 (sPD-1), PD-L1 (sPD-L1), pan-BTN3As, BTN3A1, and BTN2A1, could be candidate to predict the response to immune-checkpoint blockade therapy. We evaluated the plasma levels in a learning cohort of metastatic clear cell renal carcinoma (mccRCC) patients treated with the anti-PD-1 agent nivolumab by ad hoc developed ELISA’s. Using specific cut-offs determined…

Le basi scientifiche della cancerogenesi: “up-date”

Analysis of Ki-Ras mutations in stage I rectal carcinomas and respective regional lymph nodes.

In this work we show that the percentage of Ki-RAS mutations in codons 12 and 13 in rectal cancer are sensibly lower than in colon cancer, providing further evidence that these two kinds of tumors should be considered two different entities. Moreover, we show that the detection in regional lymph nodes of the same mutation of primary tumor might represent an indicator of lymph nodes metastasis in rectal carcinoma not detected in routine histologic examination.

Detection of free-circulating tumor DNA in plasma of patients with gastrointestinal cancer.

sj-pdf-3-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-3-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Flow cytometric DNA analysis and lysosomal cathepsins b and l in locally advanced laryngeal cancer. Relationship with clinicopathologic parameters and prognostic significance

Background. The traditional factors of locally advanced laryngeal squamous cell carcinoma (LSCC) have limited predictive value for the identification of high risk patients. Therefore, it is extremely important to define prognostic factors that identify the more aggressive types. Reliable and reproducible prognostic indicators are being investigated to help clinicians identify high risk groups and address more rational treatment. Methods. Flow cytometric DNA ploidy and S-phase fraction (SPF) measurements were performed on frozen tumor tissues from a consecutive series of 71 patients with Stage III and IV LSCC. Lysosomal cathepsin B and L activity levels were determined biochemically in match…

Specific TP53 and/or Ki-ras mutations as independent predictors of clinical outcome in sporadic colorectal adenocarcinomas: results of a 5-year Gruppo Oncologico dell'Italia Meridionale (GOIM) prospective study

BACKGROUND: Although Ki-ras and TP53 mutations have probably been the genetic abnormalities most exhaustively implicated and studied in colorectal cancer (CRC) progression, their significance in terms of disease relapse and overall survival has not yet clearly been established. PATIENTS AND METHODS: A prospective study was carried out on paired tumor and normal colon tissue samples from a consecutive series of 160 previously-untreated patients, undergoing resective surgery for primary operable sporadic CRC. Mutations within the TP53 (exons 5-8) and Ki-ras (exon 2) genes were detected by PCR-SSCP analyses following sequencing. RESULTS: Mutation analyses of exons 5 to 8 of the TP53 gene showe…

Founder mutations in BRCA1 and BRCA2 genes

BRCA1 and BRCA2 germline mutations contribute to a significant number of familial and hereditary breast and/or ovarian cancers. The proportion of high-risk families with breast and/or ovarian cancer cases due to mutations in these tumor suppressor genes varies widely among populations. In some population, a wide spectrum of different mutations in both genes are present, whereas in other groups specific mutations in BRCA1 and BRCA2 have been reported with high frequency. Most of these mutations are prevalent in restricted populations as consequence of a founder effect. The comparison of haplotypes between families with the same mutation can distinguish whether high-frequency alleles derive f…

Hereditary ovarian cancer.

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the ext…

Abstract 448: Molecular analysis of BRAF gene and PTEN gene expression in metastatic colorectal cancer patients: Feasibility study

Abstract Introduction There are numerous causes triggering CRC. 25-80% of CRC shown a deregulation in Epidermal Growth Factor Receptor (EGFR) pathway. Two signaling pathways downstream of the EGFR are dysregulated in CRC the mitogen-activated protein kinase (MAPK) and the phosphoinositide-3-kinase (PI3K) pathway. Activating mutations in KRAS and BRAF (MAPK pathway) and PIK3CA affect prognosis and/or response to anti-EGFR MoAb. PTEN is a downstream effector of EGFR pathway and is involved in PI3K pathway. Loss of PTEN protein expression can occur through epigenetic silencing and mutation or allelic loss. Immunohistochemistry (IHC) is the most effective way to assay for loss of PTEN expressio…

sj-docx-1-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-1-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Exploring the Dynamic Crosstalk between the Immune System and Genetics in Gastrointestinal Stromal Tumors

Gastrointestinal Stromal Tumors (GISTs) represent a paradigmatic model of oncogene addiction. Despite the well-known impact of the mutational status on clinical outcomes, we need to expand our knowledge to other factors that influence behavior heterogeneity in GIST patients. A growing body of studies has revealed that the tumor microenvironment (TME), mostly populated by tumor-associated macrophages (TAMs) and lymphocytes (TILs), and stromal differentiation (SD) have a significant impact on prognosis and response to treatment. Interestingly, even though the current knowledge of the role of immune response in this setting is still limited, recent pre-clinical and clinical data have highlight…

Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial

Abstract Background The 8th edition of the American Joint Committee on Cancer (AJCC) staging has introduced prognostic stage based on anatomic stage combined with biologic factors. We aimed to validate the prognostic stage in HER2-positive breast cancer patients enrolled in the ShortHER trial. Methods The ShortHER trial randomized 1253 HER2-positive patients to 9 weeks or 1 year of adjuvant trastuzumab combined with chemotherapy. Patients were classified according to the anatomic and the prognostic stage. Distant disease-free survival (DDFS) was calculated from randomization to distant relapse or death. Results A total of 1244 patients were included. Compared to anatomic stage, the prognost…

Conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting tyrosine kinase inhibitor-based therapy

Abstract: Introduction: Angiogenesis is fundamental for tumor development and progression. Hence, anti-angiogenic drugs have been developed to target VEGF and its receptors (VEGFRs). Several tyrosine kinase inhibitors (TKIs) have been developed over the years and others are still under investigation, each anti-VEGFR TKI showing a different cardiotoxic profile. Knowledge of the cardiac side-effects of each drug and the magnitude of their expression and frequency can lead to a specific approach. Areas covered: This work reviews the mechanism of action of anti-VEGFR TKIs and the pathophysiological mechanisms leading to cardiotoxicity, followed by close examination of the most important drugs i…

A novel predictive biomarker of immunotherapy response in metastatic renal cell carcinoma (mRCC): The lymphocyte microRNA expression profile.

e16109 Background: Predicting which patient with metastatic renal cell carcinoma (mRCC) will benefit from immune checkpoints inhibitors (ICPIs) still remain an issue. Biological factors particular to certain individuals have a clear effect on variation in response. Emerging evidence suggests that small non-coding RNA, such as microRNAs (miRNAs), are critical modulators of numerous cellular processes, including immune surveillance. The main aim of this study was to analyze the lymphocyte miRNA expression profile in mRCC patients and dynamic changes after the treatment with ICPI, in order to investigate the molecular mechanisms and signaling pathways involved in ICPI response and their poten…

How to Deal with Second Line Dilemma in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis

Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy with chemotherapy (CT) as second line treatment for metastatic colorectal cancer (mCRC). The right sequence of the treatments in all RAS (KRAS/NRAS) wild type (wt) patients has not precisely defined. We evaluated the impact of aforementioned targeted therapies in second line setting, analyzing efficacy and safety data from phase III clinical trials. We performed both direct and indirect comparisons between anti-EGFR and anti-VEGF. Outcomes included disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), overall su…

Technical Aspects for the Evaluation of Circulating Tumor Cells (CTCs)

Liquid biopsy is considered a valid strategy to improve patients’ selection and treatment monitoring in clinical practice. Indeed Circulating Tumor Cells (CTCs) represent an important component of liquid biopsy and their clinical evaluation is becoming fundamental for a better patients’ stratification. Several techniques have been developed for CTCs isolation and enrichment and in this chapter we provide an updated overview of the main strategies that can be used.

DNA-Aneuploidy, High SPF and Specific P53 Mutations are Indipendent Prognostic Factors in Colorectal Cancer (CRC)

sj-pdf-1-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-1-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Analysis of miRNA expression profile induced by short term starvation in breast cancer cells treated with doxorubicin

// Sergio Rizzo 1, * , Antonina Cangemi 1, * , Antonio Galvano 1, * , Daniele Fanale 1 , Silvio Buscemi 2 , Marcello Ciaccio 3 , Antonio Russo 1 , Sergio Castorina 4, 5, # and Viviana Bazan 1, # 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 Department of Internal and Specialistic Medicine (DIBIMIS), Laboratory of Clinical Nutrition, University of Palermo, Palermo, Italy 3 Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnology, University of Palermo, U.O.C. Laboratory Medicine, Policlinico University Hospital, Palermo, Italy 4 Fondazione Mediterranea…

sj-pdf-2-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-2-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Role of tumor-infiltrating lymphocytes in patients with solid tumors: Can a drop dig a stone?

International audience; In recent years, multiple strategies for eliciting anti-tumor immunity have been developed in different clinical studies. Currently, immunotherapy was clinically validated as effective treatment option for many tumors such as melanoma, non-small cell lung cancer (NSCLC) and renal cell carcinoma (RCC). Some surface receptors of immune cells, called immune checkpoint receptors, may inhibit activity of proinflammatory lymphocytes, following binding with specific ligands. Cancer cells exploit these mechanisms to inactivate tumor-infiltrating lymphocytes (TILs) to escape from immunosurveillance. Among the different tumor-infiltrating immune cell populations, including leu…

Monoclonal antibodies in gastrointestinal cancers

Introduction: Among gastrointestinal cancers, colorectal and gastric neoplasms are the most frequent. The development of new targeted drugs improved the efficacy of systemic therapy in advanced stages of those malignancies. Areas covered: This review highlights the main biological processes implicated in gastrointestinal cancer development and progression, such as angiogenesis and epidermal growth factor receptor (EGFR) signaling pathway. On these bases, anti-EGFR and anti-vascular endothelial growth factor (VEGF) monoclonal antibodies in colorectal and gastric cancer are discussed. Data about further monoclonal antibodies in development are also reported. Expert opinion: The use of monoclo…

A.Mutational analysis of BRCA1 in sicilian patients at risk for inherited of reference center for the biomolecular characterizaztion of neoplasm and genetic screening of hereditary tumors

PD-L1 expression as predictive biomarker in patients with NSCLC: a pooled analysis

// Francesco Passiglia 1, * , Giuseppe Bronte 1, * , Viviana Bazan 1, * , Clara Natoli 2 , Sergio Rizzo 1 , Antonio Galvano 1 , Angela Listi 1 , Giuseppe Cicero 1 , Christian Rolfo 3 , Daniele Santini 4 , Antonio Russo 1 1 Section of Medical Oncology, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Department of Medical, Oral and Biotechnological Sciences, University “G. D’Annunzio”, Chieti, Italy 3 Phase I- Early Clinical Trials Unit, Oncology Department and Multidisciplinary Oncology Center Antwerp (MOCA), Antwerp University Hospital, Edegem, Belgium 4 Medical Oncology Department, Campus Biomedico, University of Rome, Rome, Italy * These auth…

LncRNA H19, HOTAIR and MALAT1 as prognostic molecular biomarkers in GIST

HIF-1 is involved in the negative regulation of AURKA expression in breast cancer cell lines under hypoxic conditions

Numerous microarray-based gene expression studies performed on several types of solid tumors revealed significant changes in key genes involved in progression and regulation of the cell cycle, including AURKA that is known to be overexpressed in many types of human malignancies. Tumor hypoxia is associated with poor prognosis in several cancer types, including breast cancer (BC). Since hypoxia is a condition that influences the expression of many genes involved in tumorigenesis, proliferation, and cell cycle regulation, we performed a microarray-based gene expression analysis in order to identify differentially expressed genes in BC cell lines exposed to hypoxia. This analysis showed that h…

Molecular analysis of TP53, Ki-Ras and P16 methylation status in tissue and plasma of subjects affected by gastrointestinal cancer (GIC)

BACKGROUND: Despite the improvement in detection and surgical therapy in the last years, the outcome of patients affected by colorectal carcinoma (CRC) remains limited by metastatic relapse. The aim of this study was to investigate the presence of free tumor DNA in the plasma of CRC patients in order to understand its possible prognostic role. PATIENTS AND METHODS: Ki-Ras, TP53 mutations and p16(INK4A) methylation status were prospectively evaluated in tumor tissues and plasma of 66 CRC patients. RESULTS: In 50 of the 66 primitive tumor cases (76%) at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes. Eighteen of the 50 patients presented the same…

Apoptosis: a relevant tool for anticancer therapy.

Apoptosis is a form of cell death that permits the removal of damaged, senescent or unwanted cells in multicellular organisms, without damage to the cellular microenvironment. Defective apoptosis represents a major causative factor in the development and progression of cancer. The majority of chemotherapeutic agents, as well as radiation, utilize the apoptotic pathway to induce cancer cell death. Resistance to standard chemotherapeutic strategies also seems to be due to alterations in the apoptotic pathway of cancer cells. Recent knowledge on apoptosis has provided the basis for novel targeted therapies that exploit apoptosis to treat cancer. These new target include those acting in the ext…

A headlight on liquid biopsies: a challenging tool for breast cancer management

Breast cancer is the most frequent carcinoma and second most common cause of cancer-related mortality in postmenopausal women. The acquisition of somatic mutations represents the main mechanism through which cancer cells overcome physiological cellular signaling pathways (e.g., PI3K/Akt/mTOR, PTEN, TP53). To date, diagnosis and metastasis monitoring is mainly carried out through tissue biopsy and/or re-biopsy, a very invasive procedure limited only to certain locations and not always feasible in clinical practice. In order to improve disease monitoring over time and to avoid painful procedure such as tissue biopsy, liquid biopsy may represent a new precious tool. Indeed, it represents a bas…

sj-docx-1-tam-10.1177_17588359231151845 – Supplemental material for Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay

Supplemental material, sj-docx-1-tam-10.1177_17588359231151845 for Prognostic role of soluble PD-1 and BTN2A1 in overweight melanoma patients treated with nivolumab or pembrolizumab: finding the missing links in the symbiotic immune-metabolic interplay by Lorena Incorvaia, Gaetana Rinaldi, Giuseppe Badalamenti, Alessandra Cucinella, Chiara Brando, Giorgio Madonia, Alessia Fiorino, Angela Pipitone, Alessandro Perez, Federica Li Pomi, Antonio Galvano, Valerio Gristina, Nadia Barraco, Marco Bono, Tancredi Didier Bazan Russo, Francesca Toia, Adriana Cordova, Daniele Fanale, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

New insight on immunological activation pathways of Langerhans cells, possible tolerogenic role

Langerhans cells are the prototype of antigen presenting cell, their role is to work as sentinel in the epidermis. Like every APC Langerhans cells act as bridge between innate and acquired immunity recognizing antigens into the epidermis and bringing them to drying lymph node, their work is well described by the Langerhans cell paradigm. Recently many works designed a new and amazing role of Langerhans cells in fact they often showed tolerogenic capacity, while in many cases, they seems not necessary to promote activation of acquired immunity. Anyway Langerhans cells remaining an interesting target for new vaccine strategies because of their localization in the epidermis and the ability to …

Expression level of the mammaglobin (MGB1) gene in BC:possibile index of BC progression

New findings on primary and acquired resistance to anti-EGFR therapy in metastatic colorectal cancer: Do all roads lead to RAS?

Abstract: Anti-epidermal growth factor receptor therapy with the monoclonal antibodies cetuximab and panitumumab is the main targeted treatment to combine with standard chemotherapy for metastatic colorectal cancer. Many clinical studies have shown the benefit of the addition of these agents for patients without mutations in the EGFR pathway. Many biomarkers, including KRAS and NRAS mutations, BRAF mutations, PIK3CA mutations, PTEN loss, AREG and EREG expression, and HER-2 amplification have already been identified to select responders to anti-EGFR agents. Among these alterations KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance. Liquid b…

BRCA1 genetic testing in 106 breast and ovarian cancer families from Southern Italy (Sicily): a mutation analyses.

PURPOSE: To evaluate the contribution of germline BRCA1 mutations in the incidence of hereditary and familial Breast Cancer (BC) and/or Ovarian Cancer (OC) in patients from Southern Italy (in the region of Sicily) and to identify a possible association between the higher frequency of BRCA1 mutations and a specific familial profile. EXPERIMENTAL DESIGN: A consecutive series of 650 patients with BC and/or OC diagnosed between 1999 and 2005 were recruited from the Southern Italian region of Sicily, after interview at the "Regional Reference Centre for the Characterization and Genetic Screening of Hereditary Tumors" at the University of Palermo. Genetic counselling allowed us to recruit a total…

738P Soluble PD-1, PD-L1, pan-BTN3As, BTN3A1 and BTN2A1 as predictive biomarkers of nivolumab response in patients with metastatic clear cell renal carcinoma

MicroRNAs in colorectal cancer stem cells: new regulators of cancer stemness?

Recently, the hypothesis that colorectal tumors originate from a subpopulation of cells called ‘cancer stem cells' (CSCs) or tumor-initiating cells, which exhibit stem-like features, has been confirmed experimentally in various human cancers. Several studies have confirmed the existence of colorectal CSCs (CRCSCs) and have demonstrated that this rare cell population can be isolated by the expression of specific cell surface biomarkers. MicroRNAs (miRNAs) are a class of small non-coding RNAs, which are crucial for post-transcriptional regulation of gene expression and participate in a wide variety of biological functions, including development, cell proliferation, differentiation, metabolism…

Detection and clinical relevance of free-circulating tumor DNA in blood of patients with colorectal cancer. Proceeding of ICACT Fifteenth International Congress on Anticancer Treatment February 9th 12th 2004, Paris accepted for oral presentation

What are the Cancer Risks in BRCA Carriers Apart from Those Regarding the Breast and the Ovary?

Germline mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose to familial breast and/or ovarian cancer. The lifetime risk of members of families with genetic predisposition depends on the mutations of susceptibility genes. BRCA1 mutations seem to confer the highest risk of developing neoplastic diseases. Apart from breast and ovarian cancer mutations in BRCA, related pathways are supposed to confer a smaller risk for additional cancers (colon, melanoma, pancreas, lymphoma, prostate, liver). All these tumors have an inherited component not necessarily associated with genetic susceptibility to BRCA genes. To date he main focus of this review has been argued still with difficulty…

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in metastatic melanoma patients?

e14035 Background: The immune response to melanoma has been shown to be locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk (infiltrating the entire base of the invasive tumor), non-brisk (infiltrating only focally) and absent. Several studies showed that greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and a higher survival rate. Since recent studies revealed an association between PD-1/PD-L1 expression levels and tumor response, the aim of our study was to investigate the correlation between plasma PD-1 and presence/absence/class of TILs in metastatic melanoma patients. Methods: The plasm…

Kirsten ras mutations in patients with colorectal cancer: the 'RASCAL II' study

Researchers worldwide with information about the Kirsten ras (Ki-ras) tumour genotype and outcome of patients with colorectal cancer were invited to provide that data in a schematized format for inclusion in a collaborative database called RASCAL (The Kirsten ras in-colorectal-cancer collaborative group). Our results from 2721 such patients have been presented previously and for the first time in any common cancer, showed conclusively that different gene mutations have different impacts on outcome, even when the mutations occur at the same site on the genome. To explore the effect of Ki-ras mutations at different stages of colorectal cancer, more patients were recruited to the database, whi…

Mutational analysis of BRCA1 gene in sicilian patients at risk for inherited breast and/or ovarian cancer: experience of reference centre for the biomolecular characterization of neoplasms and genetic screening of hereditary tumors.

Gastrointestinal Stromal Tumors (GISTs)

Gastrointestinal stromal tumors (GISTs) are a group of tumors that, over the past 15 years, has emerged from a poorly understood neoplasm to a well-defined tumor entity. GISTs are highly resistant to conventional chemotherapy and, in the past, were typically managed surgically.

Navigating the liquid biopsy Minimal Residual Disease (MRD) in Non-Small Cell Lung Cancer: Making the Invisible Visible.

Liquid biopsy has gained increasing interest in the growing era of precision medicine as minimally invasive technique. Recent findings demonstrated that detecting minimal or molecular residual disease (MRD) in NSCLC is a challenging matter of debate that need multidisciplinary competencies, avoiding the overtreatment risk along with achieving a significant survival improvement. This review aims to provide practical consideration for solving data interpretation questions about MRD in NSCLC thanks to the close cooperation between biologists and oncology clinicians. We discussed with a translational approach the critical point of view from benchside, bedside and bunchside to facilitate the fut…

sj-docx-9-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-9-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

20P Is evaluation of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutational status on circulating tumour DNA (ctDNA) by liquid biopsy ready for prime-time? A systematic review and an individual patient meta-analysis

Non-coding RNAs Functioning in Colorectal Cancer Stem Cells

In recent years, the hypothesis of the presence of tumor-initiating cancer stem cells (CSCs) has received a considerable support. This model suggested the existence of CSCs which, thanks to their self-renewal properties, are able to drive the expansion and the maintenance of malignant cell populations with invasive and metastatic potential in cancer. Increasing evidence showed the ability of such cells to acquire self-renewal, multipotency, angiogenic potential, immune evasion, symmetrical and asymmetrical divisions which, along with the presence of several DNA repair mechanisms, further enhance their oncogenic potential making them highly resistant to common anticancer treatments. The main…

Beyond evidence-based data: Scientific rationale and tumor behavior to drive sequential and personalized therapeutic strategies for the treatment of metastatic renal cell carcinoma

The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC). This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to a…

TP53 mutations and microsatellite instability are prognostic factors in gastric cancer?

Can the plasma PD-1 levels predict the presence and efficiency of tumor-infiltrating lymphocytes in patients with metastatic melanoma?

Background: The immune response in melanoma patients is locally affected by presence of tumor-infiltrating lymphocytes (TILs), generally divided into brisk, nonbrisk, and absent. Several studies have shown that a greater presence of TILs, especially brisk, in primary melanoma is associated with a better prognosis and higher survival rate. Patients and Methods: We investigated by enzyme-linked immunosorbent assay (ELISA) the correlation between PD-1 levels in plasma and the presence/absence of TILs in 28 patients with metastatic melanoma. Results: Low plasma PD-1 levels were correlated with brisk TILs in primary melanoma, whereas intermediate values correlated with the nonbrisk TILs, and hig…

The effects of enzalutamide and abiraterone on skeletal related events and bone radiological progression free survival in castration resistant prostate cancer patients: An indirect comparison of randomized controlled trials.

Two new drugs, the CYP17 inhibitor abiraterone acetate and the androgen receptor (AR) antagonist enzalutamide, have recently shown to prolong OS prior chemotherapy or in docetaxel treated mCRPC patients, using steroidal therapy or placebo as control group. Updated analyses underlined the role of these new agents on two prostate-specific endpoints as radiographic progression-free survival (rPFS) and time to first skeletal-related event (tSRE). On the basis of these reports, we made an indirect comparison between abiraterone and enzalutamide. We obtained a clinically but not significant difference favouring enzalutamide over abiraterone in terms of rPFS (HR 0.48, 95% CI 0.22–1.02). No signi…

Immunological Aspects of Von Hippel-Lindau Disease: A Focus on Neuro-Oncology and Myasthenia Gravis

Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that predisposes affected individuals to a variety of malignant and benign neoplasms. The pathogenetic turning point of this illness is the accumulation of hypoxia-inducible factor (HIF)-1α, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses. From an oncological perspective, increased awareness of the molecular pathways underlying this disease is bringing us closer to the development of specific and targeted therapies. Meanwhile, on the surgical side, improved understanding can help to better identify the patients…

sj-docx-4-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-4-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Anti-endothelin drugs in solid tumors

Importance of the field: The endothelin (ET) axis, which includes the biological functions of ETs and their receptors, has played a physiological role in normal tissue, acting as a modulator of vasomotor tone, tissue differentiation and development, cell proliferation and hormone production. Interestingly, it also functions in the growth and progression of various tumors. Several researchers have identified the blockade of the ET-1 receptor as a promising therapeutic approach. Areas covered in this review: The clinical investigation of an orally bioavailable ET antagonist, atrasentan, in prostate cancer, is encouraging. In this neoplasia, it has shown antitumor activity, bone metastasis con…

The Emerging Therapeutic Landscape of ALK Inhibitors in Non-Small Cell Lung Cancer.

The treatment of metastatic non-small cell lung cancer (NSCLC) has undergone a paradigm shift over the last decade. Better molecular characterization of the disease has led to the rapid improvement of personalized medicine and the prompt delivery of targeted therapies to patients with NSCLC. The discovery of the EML4-ALK fusion gene in a limited subset of patients affected by NSCLC and the subsequent clinical development of crizotinib in 2011 has been an impressive milestone in lung cancer research. Unfortunately, acquired resistances regularly develop, hence disease progression occurs. Afterward, modern tyrosine kinase inhibitors (TKIs), such as ceritinib, alectinib, brigatinib, and lorlat…

sj-docx-2-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-2-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

BRCA1/2 pathogenic variants in triple-negative versus luminal-like breast cancers: genotype–phenotype correlation in a cohort of 531 patients

Background: Several available data suggest the association between specific molecular subtypes and BRCA1/2 mutational status. Previous investigations showed the association between BRCA1/2 pathogenic variants (PVs) in specific genomic regions and phenotypic variations of cancer relative risk, while the role of PV type and location in determining the breast cancer (BC) phenotypic features remains still unclear. The aim of this research was to describe the germline BRCA1/2 PVs in triple-negative breast cancer (TNBC) versus luminal-like BC and their potential leverage on BC phenotype. Patients &amp; methods: We retrospectively collected and analyzed all clinical information of 531 patients wit…

How Much of Familial Breast Cancer Risk is Currently Explained by the Known Genes?

The need to answer the question “how much of the familial risk is currently explained by the known genes?” has increased ,and although BRCA1 and BRCA2 are considered the two major breast cancer (BC) susceptibility genes, they do not justify the entire percentage of all hereditary BC cases. The current consensus is that other BC predisposing genes could explain at least a portion of the remaining non-mutated familial cases, including not only other high- penetrance BC genes, but also moderate and low-penetrance genes. Considering these three different categories of genes, a gap of risk estimation in breast cancer can be observed. Moreover, different researchers tried to give significance to …

Havep53gene mutations and protein expression a different biological significance in colorectal cancer?*

p53 alterations are considered the most common genetic events in many types of neoplasms, including colorectal carcinoma (CRC). These alterations include mutations of the gene and/or overexpression of the protein. The aim of our study was to assess whether in 160 patients undergoing resective surgery for primary operable CRC there was an association between p53 mutations and protein overexpression and between these and other biological variables, such as cell DNA content (DNA-ploidy) and S-phase fraction (SPF), and the traditional clinicopathological variables. p53 mutations, identified by PCR-SSCP-sequencing analysis, were found in 68/160 patients (43%) and positive staining for p53 protei…

sj-pdf-4-tam-10.1177_17588359211018018 – Supplemental material for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses

Supplemental material, sj-pdf-4-tam-10.1177_17588359211018018 for Is there any room for PD-1 inhibitors in combination with platinum-based chemotherapy as frontline treatment of extensive-stage small cell lung cancer? A systematic review and meta-analysis with indirect comparisons among subgroups and landmark survival analyses by Valerio Gristina, Antonio Galvano, Luisa Castellana, Lavinia Insalaco, Stefania Cusenza, Giuseppa Graceffa, Federica Iacono, Nadia Barraco, Marta Castiglia, Alessandro Perez, Sergio Rizzo, Antonio Russo and Viviana Bazan in Therapeutic Advances in Medical Oncology

Monoclonal antibodies for the treatment of non-hematological tumors: a safety review

Introduction: The introduction of monoclonal antibodies (moAbs) into clinical practice revolutionized the treatment strategies in several solid tumors. These agents differ from cytotoxic chemotherapy for their mechanism of action and toxicity. By targeting specific antigens present on healthy cells and modulating immune system activity, these biological drugs are able to generate a wide spectrum of peculiar adverse events that can negatively impact on patients' quality of life. Areas covered: In this review, the main side effects associated with the use of moAbs have been described to show their incidence and current management strategies, which may drive clinicians in their daily practice.…

Direct Identification of Each Specific Mutation in Codon 12 and 13 of ci-ki-ras2 by SSCP Analysis

We compared the SSCP behaviour of the DNA fragments containing c-ki-ras 2 wild type 12 and 13 codons or each of the 12 possible point mutated sequences in these two codons. We found that a single electrophoresis condition was sufficient to distinguish each specific mutation from the other 11 and from the wild type sequence. This observation makes it possible to identify each specific mutation directly by SSCP without any need for reamplification and sequencing.

sj-docx-1-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-1-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

MOESM1 of Validation of the AJCC prognostic stage for HER2-positive breast cancer in the ShortHER trial

Additional file 1. Summary of details of studies aimed at evaluating the American Joint Committee on Cancer (AJCC) 8th edition breast cancer prognostic staging.

One shot NEPA plus dexamethasone to prevent multiple-day chemotherapy in sarcoma patients

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared and disturbing adverse events of cancer treatment associated with decreased adherence to effective chemotherapy regimens. For high-risk soft tissue sarcoma patients, receiving multiple-day chemotherapy (MD-CT), antiemetic guidelines recommend a combination of an NK 1 receptor antagonist (NK 1 -RA), a 5-HT 3 receptor antagonist (5HT 3 -RA), and dexamethasone on each day of the antineoplastic treatment. NEPA is the first oral fixed-dose combination of a highly selective NK 1 -RA, netupitant, and second-generation 5HT 3 -RA, palonosetron. So far, no data has been published in literature about the efficacy of a s…

Gastric adenomas: relationship between clinicopathological findings, Helicobacter pylori infection, APC mutations and COX-2 expression.

Gastric adenomas are rare neoplastic growths characterized by localized polypoid proliferations of dysplastic epithelium that tend to progress to infiltrating adenocarcinoma. Therefore, the identification of molecular markers that could reliably recognize adenomas at risk of progression is advocated in the clinical management. In this study we investigated, in a series of gastric adenoma specimens from an area at high risk of gastric cancer, the relationship between clinicopathological characteristics of adenoma and Helicobacter pylori infection, APC mutational status, and COX-2 and the down-stream enzyme mPGES1 expression. Helicobacter pylori infection, detected in 24%, and 33% by histolog…

167P Role of the multi-gene panel testing for detection of pathogenic variants in patients with hereditary bilateral breast cancer

sj-docx-11-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-11-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome

About 10–20% of breast/ovarian (BC/OC) cancer patients undergoing germline BRCA1/2 genetic testing have been shown to harbor Variants of Uncertain Significance (VUSs). Since little is known about the prevalence of germline BRCA1/2 VUS in Southern Italy, our study aimed at describing the spectrum of these variants detected in BC/OC patients in order to improve the identification of potentially high-risk BRCA variants helpful in patient clinical management. Eight hundred and seventy-four BC or OC patients, enrolled from October 2016 to December 2020 at the “Sicilian Regional Center for the Prevention, Diagnosis and Treatment of Rare and Heredo-Familial Tumors” of University Hospital Policlini…

Analysis of molecular mechanisms and anti-tumoural effects of zoledronic acid in breast cancer cells

Zoledronic acid (ZOL) is the most potent nitrogen-containing bisphosphonate (N-BPs) that strongly binds to bone mineral and acts as a powerful inhibitor of bone resorption, already clinically available for the treatment of patients with osteolytic metastases. Recent data also suggest that ZOL, used in breast cancer, may provide more than just supportive care modifying the course of the disease, though the possible molecular mechanism of action is still unclear. As breast cancer is one of the primary tumours with high propensity to metastasize to the bone, we investigated, for the first time, differential gene expression profile on Michigan Cancer Foundation-7 (MCF-7) breast cancer cells tre…

Flow cytometric DNA analysis of hepatic tumours on ultrasound-guided fine-needle aspirates

A study was performed on a nonconsecutive series of 51 patients in order to assess the feasibility, reliability, and usefulness of flow cytometric (FCM) DNA analysis of samples obtained from benign and malignant hepatic tumours by means of ultrasound-guided fine-needle aspiration (UG-FNA). Cytological and often histological confirmation of the nature of the lesion was obtained in all cases from an expert pathologist. For FCM DNA analysis in 32 cases, it was also possible to use samples obtained at surgery from the actual tumours. There were no post UG-FNA complications, either early or late. It was possible to perform FCM DNA analysis on 6/7 (85.7%) of the benign tumour aspirates and all 44…

sj-docx-5-tam-10.1177_17588359221110162 – Supplemental material for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis

Supplemental material, sj-docx-5-tam-10.1177_17588359221110162 for The diagnostic accuracy of PIK3CA mutations by circulating tumor DNA in breast cancer: an individual patient data meta-analysis by Antonio Galvano, Luisa Castellana, Valerio Gristina, Maria La Mantia, Lavinia Insalaco, Nadia Barraco, Alessandro Perez, Sofia Cutaia, Valentina Calò, Tancredi Didier Bazan Russo, Edoardo Francini, Lorena Incorvaia, Mario Giuseppe Mirisola, Salvatore Vieni, Christian Rolfo, Viviana Bazan and Antonio Russo in Therapeutic Advances in Medical Oncology

TP53 mutations and S-phase fraction but not DNA-ploidy are independent prognostic indicators in laryngeal squamous cell carcinoma

ToprospectivelyevaluatetheprognosticsignificanceofTP53,H-,K-,andN-Rasmutations,DNA-ploidyandS-phasefraction(SPF) in patients affected by locally advanced laryngeal squamous cell carcinoma (LSCC). Eight-one patients (median follow-up was 71 months) who underwent resective surgery for primary operable locally advanced LSCC were analyzed. Tumor DNA was screened for mutational analysis by PCR/SSCP and sequencing. DNA-ploidy and SPF were performed byflow cytometric analyses. Thirty-six patients (44%) had, at least, a mutation in the TP53 gene. Of them, 22% (8/36) had double mutations and 3% (1/36) had triplemutations.Intotal,46TP53mutationswereobserved.Themajority(41%)oftheseoccurinexon5(19/46),…

Potential Role of ANGPTL4 in the Cross Talk between Metabolism and Cancer through PPAR Signaling Pathway

The angiopoietin-like 4 (ANGPTL4) protein belongs to a superfamily of secreted proteins structurally related to factors modulating angiogenesis known as angiopoietins. At first, ANGPTL4 has been identified as an adipokine exclusively involved in lipid metabolism, because of its prevalent expression in liver and adipose tissue. This protein regulates lipid metabolism by inhibiting lipoprotein lipase (LPL) activity and stimulating lipolysis of white adipose tissue (WAT), resulting in increased levels of plasma triglycerides (TG) and fatty acids. Subsequently, ANGPTL4 has been shown to be involved in several nonmetabolic and metabolic conditions, both physiological and pathological, including …

Ductal lavage: a way of carefully tracing the breast-secreting duct

Background: Breast cancer is the most commonly diagnosed neoplasia in women after nonmelanoma skin tumors. Unfortunately, present-day diagnostic methods are unable to identify the presence of a cancer until it has been developing for several years. Currently, ductal lavage seems to represent a new method of reaching an early diagnosis of breast cancer. Materials & methods: This study analyzed 30 patients with ages ranging from 40 to 55 years; and in 26 of these patients, we were able to obtain a sufficient quantity of material for cytological and biomolecular analysis. Results & conclusion: We propose an easy, reproducible method that makes it possible to obtain a detailed map of the nipple…

TP53, Ki-Ras and P16INK4A gene molecular analysis in salivary gland tumors.

Programmed Death Ligand 1 (PD-L1) as a Predictive Biomarker for Pembrolizumab Therapy in Patients with Advanced Non–Small-Cell Lung Cancer (NSCLC)

Provide enhanced digital features for this article If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact adisrapidplus@springer.com. The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparen…

TP53 mutations and S-Phase fraction are independent prognostic indicators in locally advanced laryngeal squamous cell carcinoma

Larynx tumor is a rare neoplasia that represent only the 2% of all human tumor. In particular, the 90% of tumor that occur in this organ correspond to the laryngeal squamous cell carcinoma (LSCC). From the biomolecular point of view, it was shown that the TP53 gene mutations are the most common events observed in the early phases of LSCC carcinogenesis. However, them prognostic significance remains controversial. Besides, the prognostic significance of DNA ploidy has been well established for other solid tumors, but its role in LSCC is still controversial. The aim of this study was, therefore, to prospectively evaluate the prognostic significance of TP53 mutations, DNA-ploidy and S-phase fr…