Overcoming resistance to rapalogs in gliomas by combinatory therapies.
Authors: Grzmil M, Hemmings BA
Abstract
Glioblastoma is the most common and aggressive brain tumor type, with a mean patient survival of approximately 1year. Many previous analyses of the glioma kinome have identified key deregulated pathways that converge and activate mammalian target of rapamycin (mTOR). Following the identification and characterization of mTOR-promoting activity in gliomagenesis, data from preclinical studies suggested the targeting of mTOR by rapamycin or its analogs (rapalogs) as a promising therapeutic approach. However, clinical trials with rapalogs have shown very limited efficacy on glioma due to the development of resistance mechanisms. Analysis of rapalog-insensitive glioma cells has revealed increased activity of growth and survival pathways compensatin...
