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J Clin Oncol. 2005 Apr 10;23(11):2556-68. Epub 2005 Mar 14.

Epidermal growth factor receptor mutations, small-molecule kinase inhibitors, and non-small-cell lung cancer: current knowledge and future directions.

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  • 1Program in Cancer Biology and Genetics and the Thoracic Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. paow@mskcc.org

Abstract

PURPOSE:

Gefitinib and erlotinib are small molecules that selectively inhibit epidermal growth factor receptor (EGFR) tyrosine kinase activity. When these drugs were introduced into the clinic, the specific targets affected in human tumors were unknown. In April 2004, two groups reported that mutations in the tyrosine kinase domain of EGFR are strongly associated with gefitinib sensitivity in patients with non-small-cell lung cancer (NSCLC). We subsequently extended these findings and showed that such mutations are also associated with sensitivity to erlotinib. Here, we present current knowledge about EGFR mutations in the context of clinical trials involving gefitinib and erlotinib in NSCLC.

DESIGN:

This article reviews the rationale for targeting EGFR, the development of gefitinib and erlotinib, the discovery of EGFR mutations, and subsequent studies to define the incidence, spectrum, and functions of EGFR mutations.

RESULTS:

The discovery of EGFR mutations promises to alter the ways in which we consider and treat NSCLC.

CONCLUSION:

This information can guide practitioners and help them inform their patients about EGFR mutations and their impact on the treatment of NSCLC.

PMID:
15767641
[PubMed - indexed for MEDLINE]
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