title: Emerging function of mTORC2 as a core regulator in glioblastoma: metabolic reprogramming and drug resistance.
abstract: 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 (mTOR) signaling. mTOR kinase exists in two multi-protein complexes, namely, mTORC1 and mTORC2. These complexes differ in terms of function, regulation and rapamycin sensitivity. mTORC1 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 of mTORC2 in regulating tumor growth, metabolic reprogramming, and targeted therapy resistance in GBM, which makes mTORC2 as a critical GBM drug target.
authors.affiliation: 1 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA ; 2 Neuro-Oncology Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Si-Han
authors.initials: SH
authors.lastname: Wu
authors.affiliation: 1 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA ; 2 Neuro-Oncology Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jun-Feng
authors.initials: JF
authors.lastname: Bi
authors.affiliation: 1 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA ; 2 Neuro-Oncology Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.affiliation: 1 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA ; 2 Neuro-Oncology Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Webster K
authors.initials: WK
authors.lastname: Cavenee
authors.affiliation: 1 Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA ; 2 Neuro-Oncology Program, University of California, Los Angeles, CA 90095, USA.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Mischel
keywords: Glioblastoma; PI3K; Warburg effect; mTOR; mTORC2; metabolic reprogramming