EGFR mutation in various tissues
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Somatic mutations have been demonstrated in various tumors. EGFR mutations were first demonstrated in adenocarcinoma of the lung, and a large-scale retrospective study has clearly shown that these mutations are specifically observed in this form of the disease. Recently, possible occurrence of EGFR mutations in other tumor types including ovarian and colorectal malignancies has been reported. This raises the possibility of application of EGFR-specific tyrosine kinase inhibitors (EGFR-TKI) to the treatment of these malignancies, although broad success in this venture would depend on the frequency of such mutations. In this article, we discuss somatic mutations in various tumors as well as potential application of TKI to their treatment. Ethnic difference in the frequency of somatic mutations is another area of interest since it is closely related to clinical response to EGFR-TKIs. Preliminary studies have revealed such ethnic variations regarding EGFR mutation and gene amplification. Ethnic difference of transcriptional regulation of EGFR has also been demonstrated. We recently found a biomarker related to clinical response to EGFR-TKI that might explain the ethnic differences in response to this therapy. Various tyrosine kinases are known targets of TKIs. Thus genomics of individual patients may allow personalized target-based therapeutics.
KeywordsEGFR mutation Tyrosine kinase inhibitor Ethnicity HLA
We thank Dr. N. Thatcher (Christie Hosp NHS Trust) for personal communication with T. Kato.
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