title: Defining clinically relevant molecular subsets of lung cancer.
abstract: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), gefitinib and erlotinib, induce dramatic responses in certain patients with non-small cell lung cancer (NSCLC). As such, the drugs provide an unexpected tool to dissect clinically relevant molecular subsets of NSCLC. For example, using mutational profiling of tumor DNA from patients with sensitivity, primary resistance, and secondary resistance to these agents, we and others have demonstrated that somatic mutations in the tyrosine kinase domain of EGFR are associated with sensitivity to gefitinib and erlotinib, while mutations in KRAS, which encodes a GTPase downstream of EGFR, are associated with primary resistance. Furthermore, second site mutations in the EGFR kinase domain are commonly found in patients with acquired resistance. We are now using a variety of molecular and biological approaches to help further define molecular subsets of lung cancer that have relevance in the clinic.
authors.affiliation: Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 125, New York, NY 10021, USA. paow@mskcc.org
authors.forename: William
authors.initials: W
authors.lastname: Pao
mesh_terms: D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D011799:Quinazolines / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000077156:Gefitinib