Author/Authors :
Wei، نويسنده , , Feng and Liu، نويسنده , , Yan and Bellail، نويسنده , , Anita C. and Olson، نويسنده , , Jeffrey J. and Sun، نويسنده , , Shi-Yong and Lu، نويسنده , , Guoyue and Ding، نويسنده , , Lijuan and Yuan، نويسنده , , Changji and Wang، نويسنده , , Guangyi and Hao، نويسنده , , Chunhai، نويسنده ,
Abstract :
Mammalian target of rapamycin complex 1 (mTORC1) is frequently activated in human cancers; however, clinical trials of rapalog (the mTORC1 inhibitors) have shown that pancreatic ductal adenocarcinomas (PDACs) resist to the treatment. Rapalog treatment activated the extracellular signal-regulated kinase (ERK) pathway in K-Ras mt PDAC cells. K-Ras knockdown abolished the insulin-like growth factor-1 (IGF-1)-induced ERK pathway in the K-Ras mt PDAC cells and enhanced the therapeutic efficacy of everolimus in treating K-Ras mt PDAC cells-derived mouse xenografts. The results indicate that targeting of K-Ras mutation may lead to the development of therapies that overcome rapalog resistance in PDAC.
Keywords :
K-ras , mTORC1 , pancreatic cancer , Erk , Rapalog
