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Clinical Cancer Research 14, 2895, May 15, 2008. doi: 10.1158/1078-0432.CCR-07-2248
© 2008 American Association for Cancer Research

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Molecular Pathways

Mechanisms of Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non–Small Cell Lung Cancer

Jeffrey A. Engelman1 and Pasi A. Jänne2,3

Authors' Affiliations: 1 Massachusetts General Hospital Cancer Center; 2 Lowe Center for Thoracic Oncology Dana-Farber Cancer Institute; and 3 Departments of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Pasi A. Jänne, Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, D820A, 44 Binney Street, Boston, MA 02115. Phone: 617-632-6036; Fax: 617-582-7683; E-mail: pjanne{at}partners.org.

Abstract

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors gefitinib and erlotinib are effective therapies for non–small cell lung cancer patients whose tumors harbor somatic mutations in EGFR. All patients, however, ultimately develop resistance to these agents. Thus, there is a great need to understand how patients become resistant to develop effective therapies for these cancers. Studies over the last few years have identified two different EGFR tyrosine kinase inhibitor resistance mechanisms, a secondary mutation in EGFR, EGFR 790M, and amplification of the MET oncogene. These findings have led to clinical trials using newly designed targeted therapies that can overcome these resistance mechanisms and have shown promise in laboratory studies. Ongoing research efforts will likely continue to identify additional resistance mechanisms, and these findings will hopefully translate into effective therapies for non–small cell lung cancer patients.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2008 by the American Association for Cancer Research.