title: NSCLC: An Update of Driver Mutations, Their Role in Pathogenesis and Clinical Significance.
abstract: Lung cancer is the most common malignancy in the US and causes the most cancer-related deaths. Non-small-cell lung carcinoma (NSCLC) accounts for the majority of cases. NSCLC historically was considered one entity, reflected by platinum-based therapy as the standard of care; however, with the discovery of EGFR mutations and ALK rearrangements, the landscape of treatment has become more personalized reflecting genomic heterogeneity. The molecular basis for tumor genesis was recognized and became a new method of classification. The availability of tumor sequencing and testing for these mutations is also becoming more accessible outside of major academic institutions. Targeted therapies offer alternatives to dangerous cytotoxic chemotherapy with equal or better efficacy. With these changes, driver mutations will play an increasing role in the diagnosis and treatment of NSCLC. In this review we will examine the characteristics of several NSCLC driver mutations and gene rearrangements and emerging data on therapies directed against them.
authors.affiliation: Fellow in the Div. of Hematology/Oncology at the Alpert Medical School of Brown University.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Black
authors.affiliation: Medical oncologist at the Comprehensive Cancer Center at Rhode Island Hospital and an Assistant Professor at The Warren Alpert Medical School of Brown University.
authors.forename: Humera
authors.initials: H
authors.lastname: Khurshid
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005784:Gene Amplification / Q000502:physiology; D015321:Gene Rearrangement / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D009154:Mutation; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases
keywords: ALK; BRAF; Driver Mutation; EGFR; FGFR; MET; NSCLC; RET; ROS1; Targeted therapy