| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
A crosstalk between mitogen-activated protein kinase (MAPK) and mammalian target of Rapamycin (mTOR) signaling pathways has been reported in several cancers. We have already established pancreas-specific TGF-b receptor II (Tgfbr2) knockout mice in the context of Kras activation and the cell lines derived from these mice. The clinical and histopathologic manifestations of the mice recapitulated human pancreatic ductal adenocarcinoma (PDAC). We report here that the combination therapy using CI-1040, an inhibitor of MEK (mitogen-activated protein kinase kinase) and RAD001, an inhibitor of mTOR, inhibited cell growth of pancreatic cancer in vivo and prolonged survival in a murine model of PDAC. We found that the combination therapy significantly induced cell cycle arrest dramatically compared to the single agent. These findings suggest that the double blockade of MAPK and mTOR signaling pathways might inhibit the signal crosstalk and benefit patients with advanced pancreatic cancer.
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