2013 Fiscal Year Final Research Report

Estimation of effects of EGFR-TKI on NSCLCs by cell-based approach including CTOS

Research Project

Project/Area Number	24790829
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Respiratory organ internal medicine
Research Institution	地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所)
Principal Investigator	WATANUKI ZENTA 地方独立行政法人宮城県立病院機構宮城県立がんセンター(研究所), がん先進治療開発研究部, 特任研究員 (10626518)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	癌 / 肺癌 / EGFR-TKI
Research Abstract	EGFR-TKIs work effectively on NSCLCs with EGFR-mutations, however, most of the cases eventually develop drug resistance by acquiring an additional mutation T790M. In the present study, I aimed to establish a CTOS system; a spheroid culture system with patient derived cancer cells. Initial CTOS trial worked fine. Nevertheless, due to the relatively slow rate of tumors, I established another cell-based EGFR-TKI evaluation system. Forced expression of EGFR, either wild type or mutations, enabled K562 cells to grow and survive by the help of the EGFR-driven signals. EGFR-TKI killed the cells, in a dose-dependent manner. Among the genotypes tested, L858R was the most sensitive, whereas L858R/L790M showed resistance to the first generation TKIs. I found that EGFR-TKI-induced cell death was correlated with BIMEL induction and autophagy.