Functional coding/non-coding variants in EGFR, ROS1 and ALK genes and their role in liquid biopsy as a personalized therapy

Personalized medicine holds promise to tailor the treatment options for patients’ unique genetic make-up, behavioral and environmental background. Liquid biopsy is non-invasive technique and precise diagnosis and treatment approach. Significantly, NGS technologies have revolutionized the genomic medicine by novel identifying SNPs, indel mutations in both coding and non-coding regions and also a promising technology to accelerate the early detection and finding new biomarkers for diagnosis and treatment. The number of the bioinformatics tools have been rapidly increasing with the aim of learning more about the detected mutations either they have a pathogenic role or not. EGFR, ROS1 and ALK genes are members of the RTK family. Until now, mutations within these genes have been associated with many cancers and involved in resistance formation to TKIs. This review article summarized the findings about the mostly investigated variations in EGFR, ROS1 and ALK genes and their potential role in..... READ ARTICLE

Critical Reviews in Oncology/Hematology DOI:10.1016/j.critrevonc.2020.103113

Authors: Mahmut Cerkez Ergoren, Havva Cobanogulları, Sehime Gulsun Temel, Gamze Mocan

Review PaperKirk SmithDecember 1, 2020EGFR, ROS1, ALK, Tyrosine kinase inhibitors, Liquid biopsy, Personalized therapy

"Prognostic value of TP53 concurrent mutations for EGFR- TKIs and ALK-TKIs based targeted therapy in advanced non- small cell lung cancer: a meta-analysis "

Background: The prognostic significance of TP53 concurrent mutations in patients with epidermal growth factor receptor (EGFR)- or anaplastic lymphoma kinase (ALK)- mutated advanced non–small-cell lung cancer (NSCLC) who received EGFR-tyrosine kinase inhibitors (TKIs) or ALK-TKIs based targeted therapy remains controversial. Therefore, the present meta-analysis was performed to investigate the association between TP53 concurrent mutations and prognosis of patients with advanced NSCLC undergoing EGFR-TKIs or ALK-TKIs treatments.
Methods: Eligible studies were identified by searching the online databases PubMed, Embase, Medline, The Cochrane library and Web of Science. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to clarify the correlation between TP53 mutation status and prognosis of patients. This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.
Results: In total, 15 studies wit..... READ ARTICLE

BMC Cancer DOI:10.1186/s12885-020-06805-5

Authors: Kang Qin, Helei Hou, Yu Liang and Xiaochun Zhang*

Precision medicine against ALK-positive non-small cell lung cancer: beyond crizotinib

Patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) have favorable outcomes compared to patients presenting with diffuse metastatic disease. Recent randomized trials have demonstrated safety and efficacy signals for local ablative therapies with radiotherapy, surgery, or radiofrequency ablation for OM-NSCLC patients alongside systemic therapies. However, it remains unclear whether local ablative therapy (LAT) should be offered either upfront preceding systemic therapies or following initial systemic therapies as local consolidative therapy (LCT). Establishing optimal timing of RT and systemic therapy combinations is essential to maximize efficacy while maintaining safety. Most published randomized trial evidence surrounding the benefits of LAT and systemic therapies were generated from OM-NSCLC patients receiving cytotoxic chemotherapy agents. With increasing use of novel agents such as targeted therapies (i.e., tyrosine kinase inhibitors) and immune checkpoint inhibitors in management of metastatic NSCLC patients, LAT timing may need to be modulated based on the use of specific agents. This narrative review will discuss the current evidence on either upfront LAT or LCT for OM-NSCLC based on published trials and cohort studies. We briefly explored the possible biological mechanisms of the potential clinical advantages of either approach. This review also summarized the ongoing trials incorporating both upfront LAT and LCT, and considerations for future LAT strategies. READ ARTICLE

Medical Oncology DOI:10.1007/s12032-018-1133-4

Authors: Biagio Ricciuti, Andrea De Giglio, Carmen Mecca, Cataldo Arcuri, Sabrina Marini, Giulio Metro, Sara Baglivo, Angelo Sidoni, Guido Bellezza, Lucio Crinò and Rita Chiari

Concise Review: Resistance to Tyrosine Kinase Inhibitors in Non-Small Cell Lung Cancer: The Role of Cancer Stem Cells

Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer, the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance. The aim of this review is to elucidate the role of CSCs in the development of resistance to TKIs and its implication for the management of patients. READ ARTICLE

Stem Cells DOI:10.1002/stem.2787

Authors: Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi