Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors

Haber, D. A., Bell, D. W., Sordella, R., Kwak, E. L., Godin-Heymann, N., Sharma, S. V., Lynch, T. J., Settleman, J. (2005) Molecular targeted therapy of lung cancer: EGFR mutations and response to EGFR inhibitors. Cold Spring Harbor Symposia on Quantitative Biology, 70. pp. 419-26. ISSN 0091-7451

URL: http://www.ncbi.nlm.nih.gov/pubmed/16869779
DOI: 10.1101/sqb.2005.70.043

Abstract

Somatic mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are present in approximately 10% of non-small-cell lung cancer (NSCLC), with an increased frequency in adenocarcinomas arising in nonsmokers, women, and individuals of Asian ethnicity. These mutations lead to altered downstream signaling by the receptor and appear to define a subset of NSCLC characterized by "oncogene addiction" to the EGFR pathway, which displays dramatic responses to the reversible tyrosine kinase inhibitors gefitinib and erlotinib. The rapid acquisition of drug resistance in most cases, either through mutation of the "gateway" residue in the EGFR kinase domain or by alternative mechanisms, appears to limit the impact on patient survival. Irreversible inhibitors of EGFR display continued effectiveness in vitro against cells with acquired resistance and are now undergoing genotype-directed clinical trials. The molecular and clinical insights derived from targeting EGFR in NSCLC offer important lessons for the broader application of targeted therapeutic agents in solid tumors.

Item Type: Paper
Uncontrolled Keywords: Antineoplastic Agents therapeutic use Carcinoma Non-Small Cell Lung drug therapy genetics Clinical Trials as Topic Drug Resistance Neoplasm genetics Female Gene Amplification Humans Lung Neoplasms drug therapy genetics Male Models Molecular Mutation Oncogenes Quinazolines therapeutic use Receptor Epidermal Growth Factor antagonists & inhibitors chemistry genetics physiology
Subjects: diseases & disorders > cancer > drugs and therapies
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > EGFR
diseases & disorders > cancer > cancer types > lung cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs > Sordella lab
Depositing User: CSHL Librarian
Date: 2005
Date Deposited: 24 Apr 2012 15:57
Last Modified: 13 Mar 2013 16:05
Related URLs:
URI: http://repository.cshl.edu/id/eprint/26250

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