| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| 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.
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