The impact of genomic changes on treatment of lung cancer

Am J Respir Crit Care Med. 2013 Oct 1;188(7):770-5. doi: 10.1164/rccm.201305-0843PP.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • ErbB Receptors / genetics*
  • ErbB Receptors / therapeutic use
  • Genomics
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Molecular Targeted Therapy / methods
  • Mutation / drug effects
  • Mutation / genetics
  • Oncogene Proteins / drug effects
  • Oncogene Proteins / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Proto-Oncogene Proteins / drug effects
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins B-raf / drug effects
  • Proto-Oncogene Proteins B-raf / genetics*
  • Proto-Oncogene Proteins c-met / drug effects
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins c-ret / drug effects
  • Proto-Oncogene Proteins c-ret / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / therapeutic use
  • Receptor, ErbB-2 / drug effects
  • Receptor, ErbB-2 / genetics
  • ras Proteins / drug effects
  • ras Proteins / genetics


  • Antineoplastic Agents
  • KRAS protein, human
  • Oncogene Proteins
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • ERBB2 protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Proto-Oncogene Proteins c-ret
  • RET protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins