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 k...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.展开更多
基金supported by grants from the National Institute for Neurological Diseases and Stroke(NS73831)the National Cancer Institute(CA151819)+1 种基金The Ben and Catherine Ivy Foundation,the Defeat GBM Research Collaborative,a subsidiary of National Brain Tumor Societyby the generous donations from the Ziering Family Foundation in memory of Sigi Ziering
文摘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.
