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Int J Clin Exp Pathol 2011;4(4):403-409

Review Article
Somatic mutations of the EGF receptor and their signal transducers affect the efficacy of
EGF receptor-specific tyrosine kinase inhibitors

Noriko Gotoh

Division of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Received April 11, 2011; accepted April 19, 2011; Epub April 23, 2011, published April 30, 2011

Abstract: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer that has been the most common and most fatal cancer
worldwide. Gefitinib (IressaTM) and erlotinib (TarcevaTM), specific tyrosine kinase inhibitors (TKI) for the epidermal growth factor receptor
(EGFR), have been demonstrated to be effective for some NSCLC patients and are pioneering molecular-targeted drugs used in the clinic for
cancer. Because many studies indicate that only some patient populations benefit from these drugs, there has been an urgent need to develop
diagnostic methods to select appropriate patients for whom treatment with these drugs will be beneficial. Moreover, problems of acquired
resistance after long-term treatment with the drugs have emerged. In this review, I summarize the current understanding of the EGFR-activated
signal transduction pathway, which plays important roles in tumorigenesis, and of the molecular mechanisms that determine the sensitivity
toward EGFR-TKI.  (IJCEP1104009)

Keywords: HER, ErbB, Ras, PI-3 kinase, lung adenocarcinoma, resistance

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Address all correspondence to:
Noriko Gotoh, MD, PhD,
Division of Systems Biomedical Technology, Institute of Medical Science
University of Tokyo, 4-6-1, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Tel.: +81 3 5559 5629; Fax: +81 3 5449 5425
E-mail: ngotoh@ims.u-tokyo.ac.jp