tailieunhanh - Báo cáo khoa học: EGF receptor in relation to tumor development: molecular basis of responsiveness of cancer cells to EGFR-targeting tyrosine kinase inhibitors

The function of the epidermal growth factor receptor (EGFR) is dysregu-lated in various types of malignancy as a result of gene amplification, mutations, or abnormally increased ligand production. Therefore, the tyro-sine kinase activity of the EGFR is a promising therapeutic target. | MINIREVIEW EGF receptor in relation to tumor development molecular basis of responsiveness of cancer cells to EGFR-targeting tyrosine kinase inhibitors Kenji Takeuchi and Fumiaki Ito Department of Biochemistry Faculty of PharmaceuticalSciences Setsunan University Osaka Japan Keywords cancer epidermalgrowth factor receptor EGFR gefitinib non-smallcelllung cancer NSCLC tyrosine kinase inhibitor TKI Correspondence K. Takeuchi Department of Biochemistry Faculty of Pharmaceutical Sciences Setsunan University Hirakata Osaka 573-0101 Japan Fax 81 72 866 3117 Tel 81 72 866 3118 E-mail takeuchi@ Received 17 July 2009 revised 17 September 2009 accepted 13 October 2009 doi The function of the epidermal growth factor receptor EGFR is dysregu-lated in various types of malignancy as a result of gene amplification mutations or abnormally increased ligand production. Therefore the tyrosine kinase activity of the EGFR is a promising therapeutic target. EGFR tyrosine kinase inhibitors such as gefitinib Iressa show evident anticancer effects in patients with non-small cell lung cancer. The induction of apoptosis has been considered to be the major mechanism for these gefitinib-mediated anticancer effects. Lung cancer cells harboring mutant EGFRs become dependent on them for their survival and consequently undergo apoptosis following the inhibition of EGFR tyrosine kinase by gefitinib. Gefitinib has been shown to inhibit cell survival and growth signaling pathways such as the extracellular signal-regulated kinase 1 2 pathway and the Akt pathway as a consequence of the inactivation of EGFR. However the precise downstream signaling molecules of extracellular signal-regulated kinase 1 2 and Akt have not yet been elucidated. In this minireview we have highlighted the effect of tyrosine kinase inhibitors on members of the Bcl-2 family of proteins which are downstream signaling molecules and serve as the determinants that control .