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Biomark Med. 2009 Apr;3(2):139-51. doi: 10.2217/bmm.09.9.

Theme: oncology--molecular mechanisms determining the efficacy of EGF receptor-specific tyrosine kinase inhibitors help to identify biomarker candidates.

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Division of Systems Biomedical Technology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.


Non-small-cell lung cancer is a major subtype of lung cancer, which is the most common and fatal cancer in the world. Gefitinib (Iressa) and later erlotinib (Tarceva), specific tyrosine kinase inhibitors for EGF receptors (EGFRs), have been demonstrated to be effective for some non-small-cell lung cancer patients and used in clinics as pioneers of molecule-based targeted drugs for cancer. There has been an urgent need to develop biomarkers and to select appropriate patients who should benefit from treatment with these drugs because of the high sensitivity of target cancer cells. However, problems of acquired resistance after long-term treatment with these drugs have been recognized. Emerging evidence indicates that the efficacy of these drugs is partly dependent on somatic mutations in the EGFR. In this review, we summarize recent understandings of the molecular mechanisms that determine the efficacy of EGFR-tyrosine kinase inhibitors. Towards the end of this article, we discuss recent ongoing projects validating potential biomarkers and future prospects.


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