Mutations of the Epidermal Growth Factor Receptor Gene and Related Genes As Determinants of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Sensitivity in Lung Cancer

Overview

Journal Cancer Sci

Specialty Oncology

Date 2007 Sep 25

PMID 17888036

Citations 253

Authors

Tetsuya Mitsudomi

Yasushi Yatabe

Affiliations

Soon will be listed here.

Abstract

Recent 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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