摘要
Glioblastoma （GBM） is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin （roTOR） signaling, roTOR kinase exists in two multi- protein complexes, namely, mTORC 1 and mTORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity, mTORC 1 is well established as a cancer drug target, whereas the functions of mTORC2 in cancer, including GBM, remains poorly understood. This study reviews the recent findings that demonstrate a central function ofmTORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes mTORCZ as a critical GBM drug target.
Glioblastoma(GBM) is one of the most lethal human cancers. Genomic analyses define the molecular architecture of GBM and highlight a central function for mechanistic target of rapamycin(m TOR) signaling. m TOR kinase exists in two multiprotein complexes, namely, m TORC1 and m TORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity. m TORC1 is well established as a cancer drug target, whereas the functions of m TORC2 in cancer, including GBM, remains poorly understood. This study reviews the recent findings that demonstrate a central function of m TORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes m TORC2 as a critical GBM drug target.
基金
supported by grants from the National Institute for Neurological Diseases and Stroke(NS73831)
the National Cancer Institute(CA151819)
The Ben and Catherine Ivy Foundation,the Defeat GBM Research Collaborative,a subsidiary of National Brain Tumor Society
by the generous donations from the Ziering Family Foundation in memory of Sigi Ziering
