• Tetsuya Mitsudomi and Yasushi Yatabe.
• Department of Thoracic Surgery, Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan. mitsudom@aichi-oc.jp
• Cancer Sci. 2007 Dec 1; 98 (12): 1817-24.

AbstractRecent discovery of mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in lung adenocarcinoma greatly stimulated biomarker research on predictive factors for EGFR tyrosine kinase inhibitors (TKI), such as gefitinib and erlotinib. Although patients with activating mutations of the EGFR generally respond to EGFR TKIs very well, it is natural to assume that there is no sole determinant, considering great complexity and redundancy of the EGFR pathway. Subsequently, roles of different types of EGFR mutations or mutations of genes that are members of the EGFR pathway such as KRAS and HER2 have been evaluated. In this review, we summarize the recent findings about how mutations of the EGFR and related genes affect sensitivity to EFGR-TKIs. We also discuss molecular mechanisms of acquired resistance to EGFR-TKIs that is almost inevitable in EGFR-TKI therapy. The door for genotype-based treatment of lung cancer is beginning to open, and through these efforts, it will be possible to slow the progression of lung cancer and eventually, to decrease mortality from lung cancer.

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