| Budget Amount *help |
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2014: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Outline of Final Research Achievements |
In this project, we tried to analyze the mechanisms of EGFR-TKI and ALK-TKI resistance and to develop overcoming drugs. We performed the following experiments and obtained several new findings.
(1) We searched the EGFR binding protein and found that Aki1, a scaffold protein, interacted with EGFR and mediated EGFR-TKI resistance. We could not find out the positive relationship between Pim kinase expression and EGFR-TKI resistance. During the analysis of c-met signaling pathway for EGFR-TKI resistance, we found that a c-met inhibitor tivantinib, exhibited anti-tumor activity by inhibiting tubulin polymerization.
(2) Using patient-derived samples, we succeeded to identify several mutations that were associated with ALK-TKI resistance. Theese resistance could be overcame the second generation ALK-TKIs, such as alectinib and ceritinib.
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