title: The impact of genomic changes on treatment of lung cancer.
abstract: The remarkable success of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors in patients with EGFR mutations and ALK rearrangements, respectively, introduced the era of targeted therapy in advanced non-small cell lung cancer (NSCLC), shifting treatment from platinum-based combination chemotherapy to molecularly tailored therapy. Recent genomic studies in lung adenocarcinoma identified other potential therapeutic targets, including ROS1 rearrangements, RET fusions, MET amplification, and activating mutations in BRAF, HER2, and KRAS in frequencies exceeding 1%. Lung cancers that harbor these genomic changes can potentially be targeted with agents approved for other indications or under clinical development. The need to generate increasing amounts of genomic information should prompt health-care providers to be mindful of the amounts of tissue needed for these assays when planning diagnostic procedures. In this review, we summarize oncogenic drivers in NSCLC that can be currently detected, highlight their potential therapeutic implications, and discuss practical considerations for successful application of tumor genotyping in clinical decision making.
authors.affiliation: 1 Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; and.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Cardarella
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics* / Q000627:therapeutic use; D023281:Genomics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation / Q000187:drug effects / Q000235:genetics; D015513:Oncogene Proteins / Q000187:drug effects / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000187:drug effects / Q000235:genetics*; D019859:Proto-Oncogene Proteins c-met / Q000187:drug effects / Q000235:genetics; D051096:Proto-Oncogene Proteins c-ret / Q000187:drug effects / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000187:drug effects / Q000235:genetics; D018631:ras Proteins / Q000187:drug effects / Q000235:genetics
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D015513:Oncogene Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D019859:Proto-Oncogene Proteins c-met; D051096:Proto-Oncogene Proteins c-ret; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C000626173:ALK protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human; C099282:RET protein, human