Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial

Background: Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. Methods: FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely remov…

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

Antiangiogenic effects, safety and feasibility of two different capecitabine/Oxaliplatin-based schedules in elderly colorectal cancer patients

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…

Efficacy of weekly low-dose chemotherapy in elderly women with advanced ovarian cancer: is there an antiangiogenic effect?

13133 Background: In elderly patients decreased functionality of multiple organ systems may affect pharmacokinetics and pharmacodynamics of drugs. For this reason elderly cancer patients experience enhanced susceptibility to common chemotherapy-related adverse events. A way to prevent these effects could be metronomic chemotherapy, which is a variation of dose-dense therapy, with a cumulative dose significantly lower than maximum tolerated dose. Methods: 27 advanced ovarian cancer patients, median age 67 (range 60–86), received low dose weekly continuous chemotherapy until disease progression. All patients were treated with CBDCA AUC 2 mg/ml/min and Docetaxel 35 mg/sqm (adjusted according …

PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients

PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients wit…

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…

Abstract OT-31-01: A phase II study to evaluate the efficacy and safety of pembrolizumab plus carboplatin in BRCA-related metastatic breast cancer: PEMBRACA trial

Abstract Background Considering the high proportion of tumor-infiltrating lymphocytes (TILs) in BRCA-related breast cancer, we expect that PD-1 pathway is highly expressed and PD-1 antagonist pembrolizumab could provide clinical activity in this kind of tumor. Furthermore, BRCA-related breast cancers are known to be more sensitive to platinum-derived drugs. Thus the association between Pembrolizumab and Carboplatin in metastatic BRCA-related breast cancer seems to be active in this setting of patients. This study will evaluate the safety and the efficacy of Pembrolizumab associated with Carboplatin in BRCA mutated or with unknown mutations metastatic breast cancer patients. Study and Statis…

PML expression in soft tissue sarcoma: Prognostic and predictive value in alkylating agents/antracycline-based first line therapy

Soft tissue sarcomas are aggressive tumors representing <1% of all adult neoplasms. Aim of our study was to evaluate promyelocytic leukemia gene expression value as prognostic factor and as a factor predicting response to alkylating agents/antracycline-based first line therapy. One hundred eleven patients affected by locally advanced and metastatic soft tissue sarcoma were selected. PML expression was evaluated by immunohistochemical analysis in pathological samples and in the corresponding normal tissue from each case. PML immunohistochemical results were correlated with prognosis and with radiological response to alkylating agents/antracycline-based first line therapy. PML expression was …

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

"ONCOGENE ADDICTED SOLID TUMORS: BIOMARKERS PROGNOSTIC AND PREDICTIVE OF RESISTANCE OR SENSITIVITY TO MOLECULAR TARGETED THERAPIES IN CRC

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 &amp; 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

Bortezomib: a new pro-apoptotic agent in cancer treatment.

Bortezomib is a proteasome inhibitor. It targets the ubiquitin-proteasome pathway with subsequent inhibition of the degradation of proteins involved in cell cycle regulation and cancer cell survival. The best known molecular mechanism concerns the inhibition of IkappaB breakdown and the related stabilization of NFkappaB, thus preventing its translocation to the nucleus for the activation of downstream pathways. Bortezomib is the only drug in this class which has been approved for clinical use. It has shown an efficient antitumor effect in a phase III clinical trial (APEX) involving relapsed multiple myeloma patients. Response rate, time to progression and overall survival have been improved…

Albumin versus solvent/detergent-treated pooled plasma as replacement fluid for long-term plasma exchange therapy in a patient with primary hypertriglyceridemia and recurrent hyperlipidemic pancreatitis

BACKGROUND Chylomicronemia syndrome is a metabolic condition characterized by severe fasting hypertrigliceridemia (≥1000 mg/dL) and other clinical features including chronic abdominal pain and recurrent acute pancreatitis. In patients with acute or recurrent pancreatitis, plasma exchange (PEx) is indicated for the treatment of acute disease and prevention of recurrence. The use of plasma instead of albumin as replacement fluid has been suggested for its putative ability to replace the deficient enzyme possibly leading to better clinical improvement. CASE REPORT A 40-year-old man with chylomicronemia syndrome due to a newly identified loss-of-function mutation in the lipoprotein lipase (LPL)…

Prognostic role of human equilibrative transporter 1 (hENT1) in patients with resected gastric cancer.

Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patie…

Are erlotinib and gefitinib interchangeable, opposite or complementary for non-small cell lung cancer treatment? Biological, pharmacological and clinical aspects

Abstract: Gefitinib and erlotinib are the two anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) approved for treatment of advanced NSCLC patients. These drugs target one of the most important pathways in lung carcinogenesis and are able to exploit the phenomenon of 'oncogene addiction', with different efficacy according to EGFR gene mutational status in tumor samples. Gefitinib has been approved only for EGFR mutation bearing patients regardless the line of treatment, while erlotinib is also indicated in patients without EGFR mutation who undergo second- or third-line treatment. Some studies evaluated the main differences between these drugs both for direct comp…

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…

Sex steroids, carcinogenesis, and cancer progression

The relationship between sex steroids and cancer has been studied for more than a century. Using an original intact cell analysis, we investigated sex steroid metabolism in a panel of human cancer cell lines, either hormone responsive or unresponsive, originating from human breast, endometrium, and prostate. We found that highly divergent patterns of steroid metabolism exist and that the catalytic preference (predominantly reductive or oxidative) is strictly associated with the steroid receptor status of cells. We explored intra-tissue concentrations and profiles of estrogens in a set of human breast tumors as compared to normal mammary tissues, also in relation to their estrogen receptor s…

Co-expression of CD133+/CD44+in human colon cancer and liver metastasis

Although relatively good therapeutic results are achieved in non-advanced cancer, the prognosis of the advanced colon cancer still remains poor, dependent on local or distant recurrence of the disease. One of the factors responsible for recurrence is supposed to be cancer stem cells (CSCs) or tumor-initiating cells, which are a population of cancer cells with ability to perpetuate themselves through self-renewal and to generate differentiated cells, thought to be responsible for tumor recurrence. This study globally approach the possible role of tissue-derived stem cells in the initiation of colon cancer and its metastatic process in the liver. Fresh surgical specimens from colon cancer, no…

Male breast cancer.

Male breast cancer (MaleBC) is a rare disease, accounting for <1% of all male tumors. During the last few years, there has been an increase in the incidence of this disease, along with the increase in female breast cancer (FBC). Little is known about the etiology of MaleBC: hormonal, environmental and genetic factors have been reported to be involved in its pathogenesis. Major risk factors include clinical disorders carrying hormonal imbalances, radiation exposure and, in particular, a positive family history (FH) for BC, the latter suggestive of genetic susceptibility. Rare mutations in high-penetrance genes (BRCA1 and BRCA2) confer a high risk of BC development; low-penetrance gene mutati…

Thrombotic thrombocytopenic purpura: a review of the literature in the light of our experience with plasma exchange

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

Predictive factors of response to Sunitinib in metastatic Gastrointestinal Stromal Tumors (mGISTs): A retrospective analysis

Early stage nasal vestibule tumors: safety and efficacy of HDR brachyterapy in elderly patients

VEGF and Chromogranin A (CgA): Possible new predictive factors in management of advanced prostatic cancer (APC) in elderly patients

Comparison between gemcitabine-based combination (G) and single-agent chemotherapy (S) for elderly patients (EP) with advanced non-small cell lung cancer (NSCLC): A literature-based meta-analysis

19586 Background: It was estimated that a quarter of all patients who have a diagnosis of NSCLC worldwide are more than 70 years old. This meta-analysis tries to shed light on the controversial results of phase III trials evaluating in NSCLC EP doublets against third generation S. Methods: We performed a literature search using MEDLINE and Cochrane Library. We selected only clinical trials responding to the question of our meta-analysis. Outcomes recorded were 1-year survival rate (1-y SR), overall response rate (ORR) and haematological toxicity (HT). Fixed-effects and random-effects models were used to calculate pooled odds ratios (OR). An OR greater than 1 indicates that doublet is more …

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

Antiangiogenic scheduling of lower dose chemotherapy in elderly patients with advanced colorectal cancer

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…

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…

Clinical parameters to guide decision-making in elderly metastatic colorectal CANCER patients treated with intensive cytotoxic and anti-angiogenic therapy

// Gemma Bruera 1, 2 , Antonio Russo 3 , Antonio Galvano 3 , Sergio Rizzo 3 and Enrico Ricevuto 1, 2 1 Oncology Territorial Care, S. Salvatore Hospital, Oncology Network ASL1 Abruzzo, University of L’Aquila, L’Aquila, Italy 2 Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, L’Aquila, Italy 3 Medical Oncology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: elderly, intensive treatment, metastatic colorectal cancer, triplet chemotherapy plus bevacizumab, unfit Received: June 07, 2016     Accepted: November 24, 2016     Published:…

HER2-positive male breast cancer: an update.

Laura Ottini1, Carlo Capalbo2, Piera Rizzolo1, Valentina Silvestri1, Giuseppe Bronte3, Sergio Rizzo3, Antonio Russo31Department of Experimental Medicine, &amp;ldquo;Sapienza&amp;rdquo; University of Rome, Rome, Italy; 2Medical Oncology, IDI-IRCCS, Rome, Italy; 3Department of Surgical and Oncological Sciences, Section of Medical Oncology, University of Palermo, Palermo, ItalyAbstract: Although rare, male breast cancer (MBC) remains a substantial cause for morbidity and mortality in men. Based on age frequency distribution, age-specific incidence rate pattern, and prognostic factor profiles, MBC is considered similar to postmenopausal breast cancer (BC). Compared with female BC (FBC), MBC cas…

New molecular targets in bone metastases.

Bone metastases have a major impact on morbidity and on mortality in cancer patients. Despite its clinical relevance, metastasis remains the most poorly elucidated aspect of carcinogenesis. The biological mechanisms leading to bone metastasis establishment have been referred as " vicious circle," a complex network between cancer cells and the bone microenvironment. This review is aimed to underline the new molecular targets in bone metastases management other than bisphosphonates. Different pathways or molecules such as RANK/RANKL/OPG, cathepsin K, endothelin-1, Wnt/DKK1, Src have recently emerged as potential targets and nowadays preclinical and clinical trials are underway. The results fr…

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

Virtual Multidisciplinary Tumor Boards: A Narrative Review Focused on Lung Cancer

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualiz…

Early Skin Toxicity as a Predictive Factor for Tumor Control in Hepatocellular Carcinoma Patients Treated with Sorafenib.

Abstract Introduction. Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients. Materials and Methods. All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand–foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response …

The immunoglobulin γ marker 17 allotype and KIR/HLA genes prevent the development of chronic hepatitis B in humans

Hepatitis B virus (HBV) infection causes a self-limiting disease in most individuals. However, &lt; 10% of infected subjects develop a chronic disease. Genetic host variability of polymorphic genes at the interface of innate and acquired immunity, such as killer immunoglobulin-like receptors (KIR), their human leucocyte antigen (HLA) and IgG allotypes (GM), could explain this different clinical picture. We previously showed a protective role of the KIR2DL3 gene for the development of chronic hepatitis B (CHB), and a detrimental role of the KIR ligand groups, HLA-A-Bw4 and HLA-C2. We have expanded the previous analysis genotyping patients for GM23 and GM3/17 allotypes. The comparison of the …

Antiemetic prophylaxis containing Palonosetron (P) alone or in combination with Aprepitant (A) in the treatment of advanced soft tissue sarcoma (STS) patients with epirubicin and ifosfamide

Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab + 5-fluorouracil(5–FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The respo…

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

KIR2DL3 and the KIR ligand groups HLA-A-Bw4 and HLA-C2 predict the outcome of hepatitis B virus infection.

Killer immunoglobulin-like receptors (KIRs) regulate the activation of Natural Killer cells through their interaction with human leukocyte antigens (HLA). KIR and HLA loci are highly polymorphic and certain HLA-KIR combinations have been found to protect against viral infections. In this study we analyzed whether the KIR/HLA repertoire may influence the course of hepatitis B virus (HBV) infection. Fifty-seven subjects with chronic hepatitis B (CHB), 44 subjects with resolved HBV infection, and 60 healthy uninfected controls (HC) were genotyped for KIR and their HLA ligands. The frequency of the HLA-A-Bw4 ligand group was higher in CHB (58%) than subjects with resolved infection (23%) (crude…

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…

Low dose splenic irradiation in myelofibrosis: outcomes and toxicity of three radiation schedule

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 …

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…

Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)

Background and aim: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. Materials and Methods: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. Results: Positive hENT1 staining patients were…

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 …

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…

Temozolomide (TMZ) in radio-chemotherapy combined schedule for treatment of newly-diagnosed high-grade gliomas (HGG)

1578 Background: Temozolomide (TMZ) is an oral alkylating agent known to cross the blood-brain barrier with efficacy against HGG and a favourable safety profile compared to conventional chemotherap...

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 …

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

Biomarkers and efficacy: Are we nearly there yet?

EDITORIAL

Gene signatures in CRC and liver metastasis

Colorectal cancer (CRC) is one of the most common causes of cancer-related death with a worldwide incidence of almost a million cases annually in both males and females. The accelerated decrease in CRC incidence rates from 1998 to 2006 largely reflects the advances in diagnosis and treatment that have enabled to detect and remove precancerous polyps. However, the screening technology has not resulted in major improvements in the prognosis of patients with advanced cancer and the liver metastasis remains the major cause of death in CRC. About 25% of patients have detectable liver metastasis at diagnosis, that are classified as “synchronous” lesions and approximately 70% of patients develop a…

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…

Hepatotoxicity of systemic therapies for unresectable hepatocellular carcinoma

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

Uncoupling Protein 2 as genetic risk factor for systemic lupus erythematosus: association with malondialdehyde levels and intima media thickness

BACKGROUND Increased oxidative stress potentially leads to accelerated atherosclerosis and, consequently, cardiovascular diseases, the main cause of death in systemic lupus erythematous (SLE). To gain insight into these mechanisms, we studied the association of uncoupling protein (UCP) 2 genetic variants, gene involved in the mitochondrial production of reactive oxygen species, and oxidative stress with SLE and the presence of atherosclerosis. METHODS Genetic analysis of the UCP2 -866G/A and UCP2 Ins/Del polymorphisms was performed in 45 SLE patients and 36 healthy controls by RFLP-PCR. Oxidation status was determined by measuring malondialdehyde (MDA) levels. Presence of subclinical athero…

The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. &lt;b&gt;&lt;i&gt;Patients and Methods:&lt;/i&gt;&lt;/b&gt; Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). &lt;b&gt;&lt;i&gt;Results:&lt;…

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…

La consulenza genetica in oncologia: implicazioni biomolecolari e cliniche.

Breast cancer genome-wide association studies: there is strength in numbers.

Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-spe…

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…

Zoledronic acid induces a significant decrease of circulating endothelial cells and circulating endothelial precursor cells in the early prostate cancer neoadjuvant setting

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; Published data demonstrated that zoledronic acid (ZOL) exhibits antiangiogenetic effects. A promising tool for monitoring antiangiogenic therapies is the measurement of circulating endothelial cells (CECs) and circulating endothelial precursor cells (CEPs) in the peripheral blood of patients. Our aim was to investigate the effects of ZOL on levels of CECs and CEPs in localized prostate cancer. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Ten consecutive patients with a histologic diagnosis of low-risk prostate adenocarcinoma were enrolled and received an intravenous infusion of ZOL at baseline (T0), 28 days (T28) and 56 days (T56). Blood samp…

Promyelocytic leukemia (PML) gene expression is a prognostic factor in ampullary cancer patients

Background: Promyelocytic leukemia (PML) tumor suppressor gene plays a key role in acute PML pathogenesis but its involvement in pathogenesis and prognosis of solid cancers has not been defined yet. Patients and methods: In all, 62 ampullary adenocarcinoma patients who underwent curative surgery between 1996 and 2005 were included. Expression analysis of PML was carried out by immunohistochemical staining and correlated with disease-free survival (DFS) and overall survival (OS). Results: In 24 tumor specimens (38.7%), PML was classified as absent, in 16 (25.8%) as focally expressed and in 22 (35.5%) as diffusely expressed. By univariate analysis, DFS was significantly influenced by patholog…

“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 …

Circulating tumor DNA (ctDNA) as predictive biomarker in NSCLC patients treated with Nivolumab

Nivolumab is a programmed death-1 (PD-1)inhibitor recently approved for the treatment of NSCLC patients who failed prior chemotherapy. Searching for predictive biomarkers of immunotherapy efficacy is an area of intensive investigation for translational research. Monitoring circulating tumor DNA (ctDNA) during nivolumab treatment could help clinicians to predict the immunotherapy efficacy and ultimately improve the management of patients

Could starvation minimize chemotherapy-induced toxicities?

Background: In their recent paper Raffaghello, et al. examined the use of short-term starvation (STS) to induce differential stress resistance (DSR), that is increased protection of normal over cancer cells against chemotherapy-induced oxidative stress, using a range of model organisms. Objective/methods: We examine the results of this study and their significance. Results/conclusions: Raffaghello, et al. obtained evidence that STS induced DSR in yeast, mammalian cell cultures, and mice. It is possible that calorie restriction extends lifespan and prevents chronic diseases like tumors, by braking proliferation. We think that molecular mechanisms determining STS-induced DFS in mammals should…

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

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.

The role of second and third line tyrosine kinase inhibitor monotherapy in EGFR wild-type (and unknown mutational status) advanced non-small-cell lung cancer patients: Findings from a retrospective analysis

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 …

Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma

The molecular pathways which promote lung cancer cell features have been broadly explored, leading to significant improvement in prognostic and diagnostic strategies. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have dramatically altered the treatment approach for patients with metastatic non-small cell lung cancer (NSCLC). Latest investigations by using next-generation sequencing (NGS) have shown that other oncogenic driver mutations, believed mutually exclusive for decades, could coexist in EGFR-mutated NSCLC patients. However, the exact clinical and pathological role of concomitant genomic aberrations needs to be investigated. In this systematic review, we ai…

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%…

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…

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…

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

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

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…

Intercellular communication and human hepatocellular carcinoma.

We have previously reported that gap junction-mediated intercellular communication (GJIC) can be restored in junctionally deficient human prostate epithelial cells, also suggesting that GJIC activity is regulated by estrogen. In the present work, we report studies on sex steroid regulation of GJIC and proliferative activity in both nontumoral (Chang liver, CL) and malignant (HepG2, Huh7) human liver cells. Junctional activity and liver cell growth were measured using the scrape-loading/dye-transfer (SL/DT) and the MTS assay, respectively. Using the SL/DT, only Huh7 cells exhibited a moderate degree of Junctional activity in basic conditions, while neither CL nor HepG2 cells showed functiona…

Can the microRNA expression profile help to identify novel targets for zoledronic acid in breast cancer?

// Daniele Fanale 1, * , Valeria Amodeo 1, * , Viviana Bazan 1, * , Lavinia Insalaco 1 , Lorena Incorvaia 1 , Nadia Barraco 1 , Marta Castiglia 1 , Sergio Rizzo 1 , Daniele Santini 2 , Antonio Giordano 3 , Sergio Castorina 4, 5, # , Antonio Russo 1, # 1 Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Palermo, Italy 2 University Campus Bio-Medico, Department of Medical Oncology, Rome, Italy 3 Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA 4 Fondazione Mediterranea “G.B. Morgagni”, Catania, Italy 5 Department of Biomedic…

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…

EGFR genomic alterations in cancer: prognostic and predictive values.

The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy num…

VEGF levels could affect outcomes in elderly breast cancer women

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

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

Gemcitabine-based doublets versus single-agent therapy for elderly patients with advanced nonsmall cell lung cancer: a Literature-based Meta-analysis.

BACKGROUND: Although platinum-based combinations are considered the best option of care for patients with advanced nonsmall cell lung cancer (NSCLC), single-agent therapy is the preferred treatment for older patients. Since the late 1990s, various combinations of third-generation agents (gemcitabine [G], vinorelbine, docetaxel, and paclitaxel) have been tested, yielding contradictory results. The authors of this report performed a literature-based meta-analysis to assess the efficacy and tolerability of G-based doublets compared with single-agent chemotherapy for elderly patients with NSCLC. METHODS: Data from all published, randomized, phase 3 trials that compared a G-based doublet with a …

FULVESTRANT AND CAPECITABINE IN ELDERLY ADVANCED BREAST CANCER PATIENTS: THE PROPOSAL FOR AN EFFECTIVE AND SAFE COMBINED TREATMENT SCHEDULE.

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…

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…

Non-Pegylated Liposomal Doxorubicin/Cyclophosphamide-based schedule As Antiangiogenic Treatment In Elderly Women With Advanced Breast Cancer

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…

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

SAFETY AND EFFICACY OF INHALED IL-2 THERAPY IN PRE-TREATED BREAST CANCER ELDERLY PATIENTS WITH PULMONARY METASTASES.

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…

Impact of phospho-Akt expression on the clinical outcome and activity of gemcitabine and Akt inhibitors in pancreatic ductal adenocarcinoma

Background: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid tumors. Despite extensive preclinical and clinical research, the prognosis of this disease has not significantly improved, with a 5-year survival rate around 7%. There is an urgent need to better understand the molecular pathology of PDAC in order to improve patient selection for current treatment options and to develop novel therapeutic strategies. The PI3K/AKT/mTOR pathway plays a crucial role in PDAC: activation of Akt is a frequent event and has been correlated to poor prognosis and resistance to chemotherapy. Against this background, effective blockage of Akt signaling can lead to programmed cell death a…

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

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…

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…

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…

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…

A literature-based meta-analysis of the comparison between Gemcitabine-based combination and monochemotherapy for the treatment of advanced non-small cell lung cancer in elderly patients

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.

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

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…

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…

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…

What can platinum offer yet in the treatment of PS2 NSCLC patients? A systematic review and meta-analysis

Abstract: Background: Randomized phase III trials showed interesting, but conflicting results, regarding the treatment of NSCLC, PS2 population. This meta-analysis aims to review all randomized trials comparing platinum-based doublets and single-agents in NSCLC PS2 patients. Materials and methods: Data from all published randomized trials, comparing efficacy and safety of platinum-based doublets to single agents in untreated NSCLC, PS2 patients, were collected. Pooled ORs were calculated for the 1-year Survival-Rate (ly-SR), Overall Response Rate (ORR), and grade 3-4 (G3-4) hematologic toxicities. Results: Six eligible trials (741 patients) were selected. Pooled analysis showed a significan…

Predicting efficacy and toxicity in the era of targeted therapy: focus on anti-EGFR and anti-VEGF molecules

The treatment of solid malignancies includes various target drugs, such as monoclonal antibodies and tyrosine kinase inhibitors, which exert their effect alone or in combination with chemotherapy. The main part of these molecules have a target on proteins of EGFR and VEGF pathways. The particular toxicity profile and the financial impact, deriving from the application of these agents in cancer treatment, prompted a lot of researches to define predictive factors of their efficacy. Various biomarker were identified among the components of the targeted pathways. However just few studies allowed to identify specific factors to predict the toxicity of these drugs. In this review EGFR and VEGF-re…

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

The role of second-line tyrosine kinase inhibitor monotherapy in EGFR wild-type advanced non-small-cell lung cancer patients: Findings from a retrospective analysis.

e19030 Background: Second-line treatment for advanced non-small-cell lung cancer (aNSCLC) patients includes monotherapy with a third generation cytotoxic drug (CT) or with the tyrosine kinase inhib...

The role of macrophages polarization in predicting prognosis of radically resected gastric cancer patients

Tumour-associated Macrophages (TAM) present two different polarizations: classical (M1) characterized by immunostimulation activity and tumour suppression; alternative (M2) characterized by tumour promotion and immune suppression. In this retrospective study, we evaluated the correlation between the two forms of TAM with survival time in radically resected gastric cancer patients. A total of 52 chemo- and radio- naive patients were included. Two slides were prepared for each patient and double-stained for CD68/NOS2 (M1) or CD68/CD163 (M2) and five representative high-power fields per slide were evaluated for TAM count. The median value of the two macrophage populations density and the media…

Virtual Multidisciplinary Tumor Board: A Narrative Review Focused on Lung Cancer

Article full text The above summary slide represents the opinions of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online (see “read the peer-reviewed publication” opposite). © The authors, CC-BY-NC 2021.