FGFR a promising druggable target in cancer: Molecular biology and new drugs.

Abstract: Introduction: The Fibroblast Growth Factor Receptor (FGFR) family consists of Tyrosine Kinase Receptors (TKR) involved in several biological functions. Recently, alterations of FGFR have been reported to be important for progression and development of several cancers. In this setting, different studies are trying to evaluate the efficacy of different therapies targeting FGFR. Areas Covered: This review summarizes the current status of treatments targeting FGFR, focusing on the trials that are evaluating the FGFR profile as inclusion criteria: Multi-Target, Pan-FGFR Inhibitors and anti-FGF (Fibroblast Growth Factor)/FGFR Monoclonal Antibodies. Expert opinion: Most of the TKR share …

Moving osimertinib to first-line: the right “strategy” in the chessboard of epidermal growth factor receptor-mutated non-small cell lung cancer?

In the N Engl J Med , Soria and colleagues have recently reported the results of the phase III randomized FLAURA trial (1), comparing osimertinib with first generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) gefitinib or erlotinib in treatment-naive patients with advanced non-small cell lung cancer (NSCLC) and activating EGFR -mutations.

The Synergistic Effect of SAHA and Parthenolide in MDA-MB231 Breast Cancer Cells

The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagic activity…

Vaccine and immune cell therapy in non-small cell lung cancer

Abstract: Despite new advances in therapeutics, lung cancer remains the first cause of mortality among different types of malignancies. To improve survival, different strategies have been developed such as chemotherapy combinations, targeted therapies and more recently immunotherapy. Immunotherapy is based on the capability of the immune system to differentiate cancer cells from normal cells to fight against the tumor. The two main checkpoint inhibitors that have been widely studied in non-small cell lung cancer (NSCLC) are PD-1/PD-L1 and CTLA-4. However, interactions between tumor and immune system are much more complex with several different elements that take part and probably many new i…

In silico pathway analysis in cervical carcinoma reveals potential new targets for treatment

Abstract: An in silico pathway analysis was performed in order to improve current knowledge on the molecular drivers of cervical cancer and detect potential targets for treatment. Three publicly available Affymetrix gene expression data-sets (GSE5787, GSE7803, GSE9750) were retrieved, vouching for a total of 9 cervical cancer cell lines (CCCLs), 39 normal cervical samples, 7 CIN3 samples and 111 cervical cancer samples (CCSs). Predication analysis of microarrays was performed in the Affymetrix sets to identify cervical cancer biomarkers. To select cancer cell-specific genes the CCSs were compared to the CCCLs. Validated genes were submitted to a gene set enrichment analysis (GSEA) and Expre…

Targeting Angiogenesis in Biliary Tract Cancers: An Open Option

Abstract: Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and…

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

Central nervous system involvement in ALK-rearranged NSCLC : promising strategies to overcome crizotinib resistance

ABSTRACT: Introduction: ALK rearranged Non Small Cell Lung Cancers (NSCLCs) represent a distinct subgroup of patients with peculiar clinic-pathological features. These patients exhibit dramatic responses when treated with the ALK tyrosine kinase inhibitor Crizotinib, albeit Central Nervous System (CNS) activity is much less impressive than that observed against extracranial lesions. CNS involvement has become increasingly observed in these patients, given their prolonged survival. Several novel generation ALK inhibitors have been developing to increase CNS penetration and to provide more complete ALK inhibition. Areas covered: The CNS activity of Crizotinib and novel generation ALK inhibito…

Can curcumin induces selective packaging of miRNAs in exosomes? A pilot study in chronic myelogenous leukemia cells.

e13563 Background: Chronic myeloid leukemia is a myeloproliferative disorder that comes from a hematopoietic stem cell or a multipotent progenitor. Exosomes are biological nanovescicles (40-100 nm)...

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…

Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targe…

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

Improvement in Lung Cancer Outcomes With Targeted Therapies: An Update for Family Physicians.

Abstract: In the past decade the advent of target therapy has led to a silent revolution in the treatment of lung cancer. Thanks to the specificity of their target, new tailored drugs are able to achieve a larger benefit and lower toxicity and provide better quality of life than cytotoxic drugs in a limited number of patients, selected by molecular profile. Nowadays, the epidermal growth factor receptor tyrosine kinase inhibitors erlotinib and gefitinib, and the anaplastic lymphoma kinase inhibitor crizotinib, are targeted agents approved for treatment of non-small-cell lung cancer. Family physicians play an important role in the treatment, detection, and management of common toxicities and…

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…

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

Abstract: Prostate cancer is the second most diagnosed cancer in males in the world. Plasma quantification of prostate-specific antigen substantially improved the early detection of prostate cancer, but still lacks the required specificity. Clinical management of prostate cancer needs advances in the development of new non-invasive biomarkers, ameliorating current diagnosis and prognosis and guiding therapeutic decisions. microRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post-transcriptional level. These miRNAs are expressed in the cells and are also present in cell-derived extracellular vesicles such as exosomes. Exosomes have been shown to act as…

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

The role of targeted therapy for gastrointestinal tumors

Abstract: Many targeted drugs have been studied to target the molecular pathways involved in the development of gastrointestinal cancers. Anti-VEGF, anti-EGFR agents, and recently also multi-kinase inhibitor regorafenib, have already been available for the treatment of metastatic colorectal cancer patients. To date, Her-2 positive, gastric cancer patients, are also treated with trastuzumab, while the multi-targeted inhibitor, sorafenib, represents the standard treatment for hepatocellular carcinoma patients. Finally, sunitinib and everolimus, have been approved for the treatment of the neuroendocrine gastroenteropancreatic tumors. Actually a great number of further drugs are under preclinic…

Exosome-mediated drug resistance in cancer: the near future is here.

Drug resistance exerts a crucial role in several cancer treatments. Understanding the resistance mechanisms against different therapeutic agents can be helpful to determine the prognosis, but remains a tricky task. In this context, tumor-derived exosomes (TDEs) may give crucial answers about these resistance mechanisms. Exosomes are biological nanovesicles with an average size around 30–100 nm of diameter (Figure 1) that originate from the endocytic pathway by the inward budding of multivesicular bodies (MVB), and they function as cell-free messengers, involved in the cell–cell communication [Kowal et al. 2014]. It has been demonstrated that both cells in physiological and pathological cond…

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…

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

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…

Management of Toxicity Induced by Anti-EGFR Therapy in Metastatic Colorectal Cancer

Use of anti-epidermal growth factor receptor (anti-EGFR) agents has yielded significant advances in the treatment of patients with metastatic colorectal cancer. In fact these drugs, which include the monoclonal antibodies cetuximab and panitumumab, can be delivered both as a single agent and in combination with chemotherapy, achieving better survival and quality of life and in some cases also resectability of metastases. However, these agents can result in the development of toxicities that are usually different from those observed with chemotherapy alone. For the management of these adverse effects, proper knowledge is mandatory. Skin toxicity is the most frequent adverse effect. Other tox…

Cancer Clonal Evolution and Intra-tumor Heterogeneity

Despite recent advances in understanding cancer onset mechanisms and development of new therapeutic approaches, however, the resistance of tumor cells to different therapies represents the main obstacle to the successful treatment, resulting in poor prognosis and tumor recurrence. Currently, understanding the causes underlying this resistance is the main objective of oncology research in recent years. Tumors are not uniform diseases but heterogeneous entities consisting of cell populations called clones, with different genetic and molecular characteristics. Indeed, most of cancers shows usually a single clonal origin at the early stages of the disease, but, in advanced stages, tumors may in…

P1.17 How to Visualize Exosomes in NSCLC: “The New Guest Star in the Liquid Biopsy Movie”

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

Targeted Therapies in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the main causes of death in patients affected by chronic liver diseases. The awareness of the biomolecular mechanisms underlying the complex carcinogenic process led to the development of targeted molecules, which are able to block this process. Sorafenib is a tyrosine-kinase inhibitor, and currently, it is the only drug approved by the US Food and Drug Administration (FDA) for the treatment of HCC. However, some studies have demonstrated the efficacy of single drug therapies or combination therapies. They showed an improvement with regard to overall survival, time to progression, and progression-free survival, although these therapies were not free …

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

Looking for a new panacea in ALK-rearranged NSCLC: may be Ceritinib?

Abstract: In the past decade, the advent of targeted therapy led to a silent revolution in the war against lung cancer and a significant evolution on the concept of Phase I clinical trials design. Thanks to the specificity of their target, the new drugs have radically changed NSCLC treatment, leading to the development of personalized strategies. The accelerated approval of the first ALK-inhibitor, Crizotinib and more recently Ceritinib, without a Phase III randomized, clinical trial, has been an amazing success story in lung cancer research, marking the beginning of a new decade of targeted drugs development, characterized by modern, biomarker-driven, early clinical trial design and shorte…

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

Exosomes genetic cargo in lung cancer: a truly Pandora s box

Lung cancer is a highly lethal disease. Targeted therapies have been developed in last years, however survival rates are not improving due to the delay in the diagnosis, making biomarkers one of the most interesting fields of study in cancer. Liquid biopsy has raised as an alternative to tissue biopsy due to improvements in analytical techniques for circulating tumor cells (CTCs), cell free DNA and exosomes. Among all, exosomes have raised as one of the most promising tools to understand the tumor due to their stability in the blood and their similarity to the cells of origin. In the last years, different alterations have been described inside the exosomes derived from non-small cell lung c…

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

Profile of the Roche cobas® EGFR mutation test v2 for non-small cell lung cancer

Abstract: Introduction: The discovery of driver mutations in non-small cell lung cancer (NSCLC) has led to the development of genome-based personalized medicine. Fifteen to 20% of adenocarcinomas harbor an epidermal growth factor receptor (EGFR) activating mutation associated with responses to EGFR tyrosine kinase inhibitors (TKIs). Individual laboratories' expertise and the availability of appropriate equipment are valuable assets in predictive molecular pathology, although the choice of methods should be determined by the nature of the samples to be tested and whether the detection of only well-characterized EGFR mutations or rather, of all detectable mutations, is required.Areas covered:…

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...

ANGIOMET: Analysis of the correlations between angiogenic markers and outcome in patients (p) with advanced nonsquamous NSCLC (NS-NSCLC) treated with carboplatin, paclitaxel, and bevacizumab (CPB).

e19014 Background: In NS-NSCLC CPB achieved median OS > 1 y and supported use of B. A broad range of predictive/prognostic markers explored for B use. In VEGF pathway ligands and receptors play an ...

Molecular target therapy for bone metastasis : starting a new era with denosumab, a RANKL inhibitor

Abstract: Introduction: The skeleton is generally the primary, and sometimes the only, site of metastasis in patients with advanced solid tumors. Bone metastases are the most frequent cause of cancer-related pain and the origin of severe morbidity in patients. Among the treatment options available for the prevention of skeletal-related events (SREs) associated with bone metastasis, zoledronic acid, an antiresorptive treatment from the group of bisphosphonates, is currently the standard of care in this setting. Areas covered: Zoledronic acid, together with denosumab (a monoclonal antibody against the receptor activator of nuclear factor kappa B ligand), is the most frequent approach for the …

Corrigendum to “Liquid biopsies in lung cancer: The new ambrosia of researchers” [Biochem. Biophys. Act. 1846(2014) 539–546]

a Phase I — Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium b Molecular Pathology Unit, Pathology Department, Antwerp University Hospital, Wilrijkstraat 10, Edegem 2650, Belgium c Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology, University of Palermo, Via Liborio Giuffre 5, Palermo 90127, Italy d Department of Investigational Cancer Therapeutics (Phase I Program), The University of Texas MD Anderson Cancer Center, Holcombe Blvd 1400, Unit 455, Houston 77030, USA e Department of Biopathology and Medical and Forensic Biotechnologies, Section of Biology and Genetics, University of Palermo, V…

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

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

Epithelial-to-mesenchymal transition in the context of epidermal growth factor receptor inhibition in non-small-cell lung cancer

The identification of oncogenic driver mutations in non-small-cell lung cancer (NSCLC) has led to the development of targeted drugs. Tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) target lung tumours bearing EGFR-activating mutations. This new therapeutic strategy has greatly improved tumour response rates. However, drug resistance invariably occurs during TKI-based treatment. Epithelial-to-mesenchymal transition (EMT) is one of the resistance mechanisms identified in EGFR-mutated NSCLC treated with TKIs. In this review we gather together the most important findings on this phenomenon in relation to cancer stem cells and cancer epigenetics. We…

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

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 …

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

VIPoma and PPoma

Gastrinomas are rare tumors of the neuroendocrine system, occurring within the pancreas and duodenum. The annual incidence is estimated at 0.5 per million of the population [1]. Overproduction of gastrin by these tumors produces a sustained increase in gastric acid secretion, leading to clinical manifestations of complicated peptic ulcer disease known as the Zollinger-Ellison syndrome (ZES) [2]. Although most gastrinomas grow slowly, over 60 % are malignant and 25 % show rapid aggressive behavior [3-5]. Most commonly gastrinomas metastasize to regional lymph nodes and the liver, and it is this malignant potential which has become increasingly important since the introduction of effective me…

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…

ALK and crizotinib: After the honeymoon...what else? Resistance mechanisms and new therapies to overcome it

The last few decades have witnessed a silent revolution in the war against NSCLC, thanks to the discovery of “oncogenic drivers” and the subsequent development of targeted therapies. The discovery of the EML4-ALK fusion gene in a subgroup of patients with NSCLC and the subsequent clinical development of crizotinib has been an amazing success story in lung cancer translational-research, and its accelerated approval [only 4 years from the discovery of ALK rearrangement in NSCLC to the approval by the Food and Drug Administration (FDA)] marked the beginning of the new decade of targeted therapy. However, common to all targeted therapies, despite an initial benefit, patients inevitably experien…

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

How to find the Ariadne's thread in the labyrinth of salvage treatment options for metastatic colorectal cancer?

Abstract: Since a chance for cure was found out in metastatic colorectal cancer (mCRC) patients undergoing a resection of liver and lung metastases, high tumor shrinkage by chemotherapy regimens and their combination with targeted agents have been addressed in potentially resectable mCRC. However, most mCRC patients cannot reach this opportunity because of tumor burden or metastatic sites. For these patients a salvage systemic therapy could be offered to prolong survival. To date, a huge number of clinical trials provided some evidences for the achievement of this goal. A lot of chemotherapeutic regimens in combination with biological therapies are now available. We tried to propose a simpl…

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…

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

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

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…

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

Follow up analysis by exosomal miRNAs in EGFR mutated non-small cell lung cancer (NSCLC) patients during osimertinib (AZD9291) treatment: A potential prognostic biomarker tool.

e23035Background: NSCLC patients harboring EGFR mutations are able to receive approved tyrosine kinase inhibitors (TKIs) but to better assess the treatment responses new tools are needed. Liquid bi...

Liquid Biopsy in Prostate Cancer

Chemotherapy is no longer the only therapeutic option for the treatment of advanced prostate cancer. The understanding of the pathophysiological mechanisms and its dynamic changes has divided neoplastic progression into different moments. Indeed prostate cancer changes over time from a state where cell proliferation is hormone-dependent to a stage where cell growth is hormone-independent (castration resistant disease, mCRPC). This knowledge has allowed the development of new generation hormonal agents that, along with the advent of new chemotherapeutic agents, have changed the long-term prognosis of this disease. As a result, the progression of prostate disease is dynamic over time and its …

Cancer and the microbiome : potential applications as new tumor biomarker

Abstract: Microbial communities that colonize in humans are collectively described as microbiome. According to conservative estimates, about 15% of all types of neoplasms are related to different infective agents. However, current knowledge is not sufficient to explain how the microbiome contributes to the growth and development of cancers. Large and thorough studies involving colonized, diverse and complex microbiome entities are required to identify microbiome as a potential cancer marker and to understand how the immune system is involved in response to pathogens. This article reviews the existing evidence supporting the enigmatic association of transformed microbiome with the developmen…

Use of the word "cured" for cancer patients-implications for patients and physicians: the Siracusa charter

Long-term survival for adult patients with solid tumours continues to increase. For some cancers, the possibility of recurrence after a number of years is extremely low, and the risk of death becomes similar to that of the general population of the same sex and age. During the Fifth European Conference on Survivors and Chronic Cancer Patients held in Siracusa, Italy, June 2014, oncologists, general practitioners, epidemiologists, cancer patients and survivors, and patient advocates joined to discuss the possible use of the term “cured” in reference to some adult patients with solid tumours. The specific focus was the appropriateness of using the term in communicating with cancer patients, s…

Upfront radiation versus EGFR-TKI : which is the best approach for EGFR-mutated NSCLC patients with brain metastasis?

In The Journal of Clinical Oncology , William J. Magnuson (1) and colleagues have recently reported the results of a multicenter retrospective analysis comparing the impact of three different treatment strategies on survival outcomes of 351 patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) and brain metastases (BM). Treatment options included stereotactic radiosurgery (SRS) followed by EGFR-TKI (n=100), whole-brain radiotherapy (WBRT) followed by EGFR-TKI (n=120), or EGFR-TKI followed by SRS or WBRT at the time of intracranial progression (n=131). Results showed a significantly longer median overall survival (OS) in patients who received upfron…

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.

The inhibitor of differentiation-1 (Id1) enables lung cancer liver colonization through activation of an EMT program in tumor cells and establishment of the pre-metastatic niche

Abstract: Id1 promotes carcinogenesis and metastasis, and predicts prognosis of non-small cell lung cancer (NSCLC)-adenocarcionoma patients. We hypothesized that Id1 may play a critical role in lung cancer colonization of the liver by affecting both tumor cells and the microenvironment. Depleted levels of Id1 in LLC (Lewis lung carcinoma cells, LLC shId1) significantly reduced cell proliferation and migration in vitro. Genetic loss of Id1 in the host tissue (Id1(-/-) mice) impaired liver colonization and increased survival of Id1 animals. Histologically, the presence of Idl in tumor cells of liver metastasis was responsible for liver colonization. Microarray analysis comparing liver tumor n…

Adjuvant Chemoradiation Therapy in Gastric Cancer: Critically Reviewing the Past and Visualizing the Next Step Forward

Gastric cancer remains one of the most common malignancies worldwide. Despite the significant advances in surgical treatment and multimodality strategies, prognosis has modestly improved over the last two decades. Locoregional relapse remains one of the main issues and the combined chemoradiation treatment seems to be one of the preferred approaches. However, more than ten years after the hallmark INT-0116 trial, minimal progress has been made both in terms of effectiveness and toxicity. Moreover, new regimens added to combined therapy failed to prove favourable results. Herein, we attempt a thorough literature review comparing pros and cons of all relative studies and potential bias, targe…

EML4-ALK translocation identification in RNA exosomal cargo (ExoALK) in NSCLC patients: A novel role for liquid biopsy

Abstract: The introduction of druggable targets has significantly improved the outcomes of non-small cell lung cancer patients (NSCLC). EML4-ALK translocation represents 4-6% of the druggable alterations in NSCLC. With the approval of Crizotinib, first discovered drug for the EML4-ALK translocation, on first line treatment for patients with detected mutation meant a complete change on the treatment landscape. The current standard method for EML4-ALK identification is immunohistochemistry or FISH in a tumor biopsy. However, a big number of NSCLC patients have not tissue available for analysis and others are not suitable fir biopsy due to their physical condition or the location of the tumor.…

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

Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition

AbstractA fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved …

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…

BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer.

Abstract: Introduction: Several new targeted agents with anti-angiogenic properties have been developed recently, including vandetanib, sunitinib, sorafenib, bevacizumab and others. Tumor development, progression, metastasis are strongly linked to angiogenesis. Targeted agents like bevacizumab, a monoclonal antibody which targets VEGF, have been fully developed in several solid tumors. These new agents strongly advocate that targeting angiogenesis is one of the best approaches for cancer therapy. Areas covered: Those agents that target additional pro-angiogenic intracellular signaling pathways beyond VEGF signaling have also the potential to contribute to anticancer therapies. The authors p…

Indications for Locoregional Tumor Therapies: CRC Liver Metastases

The liver represents the most affected site in patients affected by colorectal carcinoma (mCRC) [1]. More than half cases develop colorectal liver metastases (CLMs) during the evolution of the disease, and about one-quarter occur at the disease onset [1, 2]. To date, the standard treatment of CLM is represented by liver surgery, which has allowed to achieve interesting long-term survival rates (40-60%) [3] in reported series, while it is less than 25% for patients who do not undergo surgery [4]. Unfortunately, most patients (80%), however, are not immediately eligible for surgery [5, 6]. For these patients, surgical treatment may be administered in combination with chemotherapy regimens (+/…

Exosomes in semen: opportunities as a new tool in prostate cancer diagnosis

Abstract: Prostate cancer (PCa) is the most common cancer in men. Nowadays, it is diagnosed through the test of serum prostate-specific antigen (PSA) and rectal examination; however, there is still debate about the PSA-based diagnosis. Seminal fluid (SF), contains a high concentration of subcellular lipid-bound microparticles, traditionally termed "prostasomes", that are extracellular vesicles (EVs) released into the extracellular space by prostate gland's epithelial cells. These vesicles, first described in 1982 promote motility of sperm cells, regulation of sperm cell capacitation, acrosome reaction and immune suppression within the female reproductive tract. It was demonstrated that pros…

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

Entrectinib: a potent new TRK, ROS1, and ALK inhibitor

Abstract: Introduction: Receptor tyrosine kinases (RTKs) and their signaling pathways, control normal cellular processes; however, their deregulation play important roles in malignant transformation. In advanced non-small cell lung cancer (NSCLC), the recognition of oncogenic activation of specific RTKs, has led to the development of molecularly targeted agents that only benefit roughly 20% of patients. Entrectinib is a pan-TRK, ROS1 and ALK inhibitor that has shown potent anti-neoplastic activity and tolerability in various neoplastic conditions, particularly NSCLC. Areas covered: This review outlines the pharmacokinetics, pharmacodynamics, mechanism of action, safety, tolerability, pre-cl…

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…

The potential of neurotrophic tyrosine kinase (NTRK) inhibitors for treating lung cancer

Abstract: Introduction: Molecular alterations in neurotrophic tyrosine kinase (NTRK) genes have been identified in several solid tumors including lung cancer. Pre-clinical and clinical evidence suggested their potential role as oncogenic drivers and predictive biomarkers for targeted inhibition, leading to the clinical development of a new class of compounds blocking the NTRK molecular pathway, which are currently undner early clinical investigation. Area covered: This review describes the biology of the NTRK pathway and its molecular alterations in lung cancer. It focuses on the pre-clinical and clinical development of emerging NTRK inhibitors, which have shown very promising activity in e…

Exosomes isolation and characterization in serum is feasible in non-small cell lung cancer patients: critical analysis of evidence and potential role in clinical practice

// Simona Taverna 1,2,* , Marco Giallombardo 1,3,* , Ignacio Gil-Bazo 4 , Anna Paola Carreca 3 , Marta Castiglia 3 , Jorge Chacartegui 3 , Antonio Araujo 5 , Riccardo Alessandro 1,2 , Patrick Pauwels 6 , Marc Peeters 7 and Christian Rolfo 3 1 Department of Biopathology and Medical Biotechnology, Section of Biology and Genetics, University of Palermo, Palermo, Italy 2 Institute of Biomedicine and Molecular Immunology (IBIM), National Research Council, Palermo, Italy 3 Phase I-Early Clinical Trials Unit, Oncology Department, Antwerp University Hospital (UZA) and Center for Oncological Research (CORE) Antwerp University, Wilrijkstraat, Edegem, Antwerp, Belgium 4 Department of Oncology, Clinica…

Second-Line Treatment of Non-Small Cell Lung Cancer: Clinical, Pathological, and Molecular Aspects of Nintedanib

Abstract: Lung carcinoma is the leading cause of death by cancer in the world. Nowadays, most patients will experience disease progression during or after first-line chemotherapy demonstrating the need for new, effective second-line treatments. The only approved second-line therapies for patients without targetable oncogenic drivers are docetaxel, gemcitabine, pemetrexed, and erlotinib and for patients with target-specific oncogenes afatinib, osimertinib, crizotinib, alectinib, and ceritinib. In recent years, evidence on the role of antiangiogenic agents have been established as important and effective therapeutic targets in non-small cell lung cancer (NSCLC). Nintedanib is a tyrosine kinas…

Improving extracellular vesicles visualization: From static to motion

AbstractIn the last decade, extracellular vesicles (EVs) have become a hot topic. The findings on EVs content and effects have made them a major field of interest in cancer research. EVs, are able to be internalized through integrins expressed in parental cells, in a tissue specific manner, as a key step of cancer progression and pre-metastatic niche formation. However, this specificity might lead to new opportunities in cancer treatment by using EVs as devices for drug delivery. For future applications of EVs in cancer, improved protocols and methods for EVs isolation and visualization are required. Our group has put efforts on developing a protocol able to track the EVs for in vivo intern…

Curcumin inhibits in vitro and in vivo chronic myelogenous leukemia cells growth : a possible role for exosomal disposal of miR-21

// Simona Taverna 1 , Marco Giallombardo 1 , Marzia Pucci 1 , Anna Flugy 1 , Mauro Manno 2 , Samuele Raccosta 2 , Christian Rolfo 3 , Giacomo De Leo 1 , Riccardo Alessandro 1, 4 1 Dipartimento di Biopatologia e Metodologie Biomediche, Sezione di Biologia e Genetica, Universita di Palermo, Italy 2 Istituto di Biofisica, CNR, Palermo, Italy 3 Phase I - Early Clinical Trials Unit Oncology Department and Center of Oncological Research (CORE), University Hospital Antwerp & Antwerp University, Belgium 4 Istituto di Biomedicina e Immunologia Molecolare (IBIM), Consiglio Nazionale delle Ricerche, Palermo, Italy Correspondence to: Riccardo Alessandro, e-mail: riccardo.alessandro@unipa.it Keywords: e…

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

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…

Immune checkpoint inhibitors in lung cancer: the holy grail has not yet been found…

Lung cancer is rich in molecular complexities and driven by different abnormal molecular pathways. Personalised medicine has begun to bring new hope for the treatment of patients with lung cancer, especially non-small cell lung cancer (NSCLC). The development of molecularly targeted therapy (small molecules and monoclonal antibodies) has significantly improved outcomes in the metastatic setting for patients with NSCLC whose tumours harbour activated oncogenes such as epidermal growth factor receptor (EGFR) and translocated genes like anaplastic lymphoma kinase (ALK). In addition, immune checkpoint inhibitors have also dramatically changed the therapeutic landscape of NSCLC. In particular, m…

Immunotherapy: is a minor god yet in the pantheon of treatments for lung cancer?

Abstract: Immunotherapy has been studied for many years in lung cancer without significant results, making the majority of oncologists quite skeptical about its possible application for non-small cell lung cancer treatment. However, the recent knowledge about immune escape and subsequent cancer immunoediting has yielded the development of new strategies of cancer immunotherapy, heralding a new era of lung cancer treatment. Cancer vaccines, including both whole-cell and peptide vaccines have been tested both in early and advanced stages of non-small cell lung cancer. New immunomodulatory agents, including anti-CTLA4, anti-PD1/PDL1 monoclonal antibodies, have been investigated as monotherapy …

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

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…

Multisciplinary management of patients with liver metastasis from colorectal cancer

Abstract: Colorectal cancer (CRC) is one of the leading causes of cancer-related death. Surgery, radiotherapy and chemotherapy have been till now the main therapeutic strategies for disease control and improvement of the overall survival. Twenty-five per cent (25%) of CRC patients have clinically detectable liver metastases at the initial diagnosis and approximately 50% develop liver metastases during their disease course. Twenty-thirty per cent (20%-30%) are CRC patients with metastases confined to the liver. Some years ago various studies showed a curative potential for liver metastases resection. For this reason some authors proposed the conversion of unresectable liver metastases to res…

The role of cMET in non-small cell lung cancer resistant to EGFR-Inhibitors: Did we really find the target?

Abstract: The advent of the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represented the most important innovation in NSCLC treatment over the last years. However, despite a great initial activity, secondary mutations in the same target, or different alterations in other molecular pathways, inevitably occur, leading to the emergence of acquired resistance, in median within the first year of treatment. In this scenario, the mesenchymal-epidermal transition (cMET) tyrosine kinase receptor and its natural ligand, the hepatocyte growth factor (HGF), seem to play an important role. Indeed either the overexpression or the amplification of cMET, as well as the overexpr…

Changing the education paradigm in oncology: ESO masterclass, 17 years of continuous success

In this review, we summarize the history of the 41 Masterclasses in Clinical Oncology (MCO) organized by ESO or ESO-ESMO during the last 17 years. MCOs have been held in five different geographical regions including: a) Central Europe, b) Eastern Europe and Balkans, c) Baltic and Euroasia, d) Arab World and Southern European Countries and e) Latin America. More than 2.000 young oncologists have attended and more than 250 distinguished faculty members have actively participated. The program exposes students to sessions covering all major tumors ("big killers") and to spotlights updating information on various important cancers and related topics. Participants are able to present their own cl…

Extracellular vesicles as miRNA nano-shuttles : dual role in tumor progression

[EN] Tumor-derived extracellular vesicles (EVs) have a pleiotropic role in cancer, interacting with target cells of the tumor microenvironment, such as fibroblasts, immune and endothelial cells. EVs can modulate tumor progression, angiogenic switch, metastasis, and immune escape. These vesicles are nano-shuttles containing a wide spectrum of miRNAs that contribute to tumor progression. MiRNAs contained in extracellular vesicles (EV-miRNAs) are disseminated in the extracellular space and are able to influence the expression of target genes with either tumor suppressor or oncogenic functions, depending on both parental and target cells. Metastatic cancer cells can balance their oncogenic pote…

Dilemma in metastatic colorectal cancer: VEGF versus EGRF targeting

Abstract: The modern approach for metastatic colorectal cancer (mCRC) patients is based on the identification of oncogenic pathways, which could be targeted by specific molecules. Vascular endothelial growth factor (VEGF)- and epithelial growth factor receptor (EGFR)-related pathways represent the most important biological mechanisms for cancer development and progression. However, the most significant results by VEGF and EGFR targeting could be achieved through the combination of these drugs with standard chemotherapeutic regimens. These strategies aim to improve the resectability of liver and lung metastases. For those patients who cannot be eligible for metastases resection, a 'continuum…

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…

Targeted Therapies for Non-Small Cell Lung Cancer

The discovery of new oncogenic driver mutations and the clinical development of targeted therapies have completely changed the paradigm treatment of non-small cell lung cancer (NSCLC). Epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs), erlotinib, gefitinib, afatinib, ALK-inhibitors, crizotinib, and ceritinib, have been already approved for clinical use, benefiting many patients whose tumors harbor, respectively, EGFR or EML4-ALK molecular alterations. However, despite an initial benefit, tumor progression inevitably occurs, due to the development of acquired resistance to the targeted treatments. Several mechanisms of resistance have been identified, such as the seco…

BRAF mutations in non-small cell lung cancer : has finally Janus opened the door?

Abstract: B-Raf mutations occur in about 1-2% of non-small cell lung cancers (NSCLC). These mutations generate a permanent activation of the mitogen activated protein kinase (MAPK) pathway, which promotes tumor growth and proliferation. In the present review, we discuss B-Raf mutation epidemiology, diagnostic methods to detect B-Raf mutations, the role of B-Raf as a driver mutation and a potential therapeutic target in NSCLC. The results of clinical trials involving B-Raf or MAPK pathway inhibitors for the treatment of NSCLC are also discussed. Clinical trials evaluating B-Raf inhibitors in BRAF mutated NSCLC patients have shown promising results, and larger prospective studies are warrante…

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…

Molecular profiling of pancreatic neuroendocrine tumors (pNETS) and the clinical potential

Abstract: Introduction: Pancreatic neuroendocrine tumors (pNETs) represent a small part of pancreatic neoplasms, and the knowledge about their indolent clinical course remains a subject of investigation. They occur sporadically or as part of familial cancer syndromes and are classified by WHO in 3 categories. There is ongoing research to understand their molecular profiling and leading mutations.Areas covered: The aim of this review is to clarify the overall aspects of tumorigenesis, to expose the latest developments in understanding the course of the disease and the possible therapeutic implications of these. The review also discusses functional and non-functional pNETs and associated inhe…

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Abstract: Introduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current…

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…

Nintedanib in non-small cell lung cancer: from preclinical to approval

Angiogenesis is a driving force of a tumor’s development. Targeting this process is an attractive option, as this is a feature shared by most of the solid tumors. A lot of antiangiogenic drugs have been developed following this path, including bevacizumab, sorafenib, sunitinib, vandetanib, ramucirumab, motesanib and many others. The latest drug of this class to be approved for patients with non-small cell lung cancer (NSCLC) was nintedanib, a triple angiokinase inhibitor. This molecule targets vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF) and fibroblast growth factor (FGF) pathways, avoiding the tumor’s switch to normal escape mechanisms. The pharmacokine…

Next-Generation Sequencing in Clinical Practice

Abstract During the past few decades, Sanger sequencing represented the “gold standard” technique. In order to better define the mutational status of several genes at the same time, next-generation sequencing methodologies have been introduced in the molecular laboratory workflow. In the era of personalized medicine, this technological improvement plays a key role in the comprehensive molecular characterization of cancer patients in order to get a “tile” target therapy. For different cancer patients, different target therapies are available and different genes serve as clinical it relevant biomarkers. This chapter reviews the principal features of these novel technologies and their applicat…

P2.09:cMET in NSCLC: Expression, Amplification and Mutations: Track: Biology and Pathogenesis

Curcumin modulates chronic myelogenous leukemia exosomes composition and affects angiogenic phenotype, via exosomal miR-21

Abstract: Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility. We showed that the addition of CML control exosomes to HUVECs caused an increase in IL8 and VCAM1 levels, but Curcu-exosomes reversed these effects thus attenuating …

Exosomal miRNA analysis in Non-Small Cell Lung Cancer (NSCLC) patients' plasma through qPCR : a feasible liquid biopsy tool

Abstract: The discovery of alterations in the EGFR and ALK genes, amongst others, in NSCLC has driven the development of targeted-drug therapy using selective tyrosine kinase inhibitors (TKIs). To optimize the use of these TKIs, the discovery of new biomarkers for early detection and disease progression is mandatory. These plasma-isolated exosomes can be used as a non-invasive and repeatable way for the detection and followup of these biomarkers. One ml of plasma from 12 NSCLC patients, with different mutations and treatments (and 6 healthy donors as controls), were used as exosome sources. After RNAse treatment, in order to degrade circulating miRNAs, the exosomes were isolated with a comm…

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

Exosomes in lung cancer liquid biopsies: Two sides of the same coin?

LETTER TO EDITOR

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

Liquid Biopsy in Non-Small Cell Lung Cancer (NSCLC)

Lung cancer is the leading cause of cancer deaths worldwide. To date, the gold standard for the molecular analysis of a patient affected by NSCLC is the tissue biopsy. The discovery of activating mutations and rearrangements in specific genes has revolutionized the therapeutic approaches of lung cancer over the last years. For this reason, a strict “molecular follow-up” is mandatory to evaluate patient’s disease evolution. Indeed, liquid biopsy has raised as the “new ambrosia of researchers” as it could help clinicians to identify both prognostic and predictive biomarkers in a more accessible way. Liquid biopsy analysis can be used in different moments starting from diagnosis to relapse, ea…

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…

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

Exosomes as diagnostic and predictive biomarkers in lung cancer

The concept of exosomes has evolved from be considered garbage bags to the demonstration that exosomes could play very interesting roles and functions, from biomarkers detection to the potential of work as drug delivery systems. It has been widely proved that exosomes can contain key molecules important for the tumour development. The current review summarizes the latest investigations developed in the field of predictive exosomal biomarkers. The microRNAs (miRNAs) are the more known molecules due to their amount inside the exosomes and the sensitivity of the techniques available for their study. However, exosomal proteins, RNA and DNA are becoming an interesting and more feasible field of …

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

Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates

Locked nucleic acid (LNA) oligonucleotides have been successfully used to efficiently inhibit endogenous small noncoding RNAs in vitro and in vivo. We previously demonstrated that the direct miR-221 inhibition by the novel 13-mer LNA-i-miR-221 induces significant antimyeloma activity and upregulates canonical miR-221 targets in vitro and in vivo. To evaluate the LNA-i-miR-221 pharmacokinetics and pharmacodynamics, novel assays for oligonucleotides quantification in NOD.SCID mice and Cynomolgus monkeys (Macaca fascicularis) plasma, urine and tissues were developed. To this aim, a liquid chromatography/mass spectrometry method, after solid-phase extraction, was used for the detection of LNA-i…

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

Amphiregulin contained in NSCLC-exosomes induces osteoclast differentiation through the activation of EGFR pathway

AbstractNon-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. The majority of patients are diagnosed in advanced disease stage. Bone metastasis is the most frequent complication in NSCLC resulting in osteolytic lesions. The perfect balance between bone-resorbing osteoclasts and bone-forming osteoblasts activity is lost in bone metastasis, inducing osteoclastogenesis. In NSCLC, the epidermal growth factor receptor (EGFR) pathway is constitutively activated. EGFR binds Amphiregulin (AREG) that is overexpressed in several cancers such as colon, breast and lung. Its levels in plasma of NSCLC patients correlate with poor prognosis and AREG was recently …

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