2013 Fiscal Year Final Research Report

Dual inhibition of MAPK and mTOR signaling on Pancreatic Cancer

Research Project

Project/Area Number	23790773
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Gastroenterology
Research Institution	The University of Tokyo (2011, 2013) Saitama Medical University (2012)
Principal Investigator	MOHRI DAI 東京大学, 医学部附属病院, その他 (20582513)
Project Period (FY)	2011 – 2013
Keywords	膵発癌マウスモデル / 分子標的薬
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.

(3 results)