[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Glioblastoma-derived stem cells (GSCs) are responsible for the cancer resistance to therapies. We show here that GSC-enriched neurospheres are resistant to the treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to the insufficient expression of the death receptor DR4 and DR5 and the overexpression of cellular Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (c-FLIP). However, treatment with cisplatin leads to the upregulation of DR5 and downregulation of c-FLIP and restores TRAIL apoptotic pathway in the neurospheres. This study suggests that the combined treatment of TRAIL and cisplatin can induce apoptosis in GSCs and thus provide an effective treatment of glioblastomas.
Full-text · Article · Aug 2011 · Cancer Investigation