Please use this identifier to cite or link to this item: https://doi.org/10.3389/fphar.2016.00395
Title: Judicious toggling of mTOR activity to combat insulin resistance and cancer: Current evidence and perspectives
Authors: Ong, P.S 
Wang, L.Z
Dai, X
Tseng, S.H
Loo, S.J
Sethi, G 
Keywords: 2 (4 amino 1 isopropyl 1h pyrazolo[3,4 d]pyrimidin 3 yl) 1h indol 5 ol
2 (4 hydroxyphenyl) 4 morpholinopyrido[3',2':4,5]furo[3,2 d]pyrimidine
2 amino 8 [4 (2 hydroxyethoxy)cyclohexyl] 6 (6 methoxy 3 pyridinyl) 4 methylpyrido[2,3 d]pyrimidin 7(8h) one
4 (4 amino 5 (7 methoxy 1h indol 2 yl)imidazo[5,1 f][1,2,4]triazin 7 yl)cyclohexanecarboxylic acid
5 [2 (2,6 dimethylmorpholino) 4 morpholinopyrido[2,3 d]pyrimidin 7 yl] 2 methoxybenzenemethanol
8 (6 methoxy 3 pyridinyl) 3 methyl 1 [4 (1 piperazinyl) 3 (trifluoromethyl)phenyl] 1h imidazo[4,5 c]quinolin 2(3h) one
alpha interferon
apitolisib
azd 8055
c 115
cc 233
dactolisib
everolimus
mammalian target of rapamycin complex 1
mammalian target of rapamycin complex 2
mammalian target of rapamycin inhibitor
omipalisib
oxa 01
rapamycin
ridarolimus
sapanisertib
temsirolimus
torin1
unclassified drug
unindexed drug
vistusertib
way 600
wjd 008
wye 354
wye 687
xl 388
antineoplastic activity
cancer chemotherapy
cancer stem cell
carcinogenesis
diabetes mellitus
drug indication
drug structure
Hodgkin disease
human
insulin resistance
kidney carcinoma
large cell lymphoma
mantle cell lymphoma
mutation
neoplasm
neuroendocrine tumor
nonhodgkin lymphoma
nonhuman
ovary cancer
pathogenesis
phase 1 clinical trial (topic)
phase 2 clinical trial (topic)
phase 3 clinical trial (topic)
protein expression
protein function
protein targeting
regulatory mechanism
Review
signal transduction
structure analysis
Issue Date: 2016
Publisher: Frontiers Media S.A.
Citation: Ong, P.S, Wang, L.Z, Dai, X, Tseng, S.H, Loo, S.J, Sethi, G (2016). Judicious toggling of mTOR activity to combat insulin resistance and cancer: Current evidence and perspectives. Frontiers in Pharmacology 7 (OCT) : 395. ScholarBank@NUS Repository. https://doi.org/10.3389/fphar.2016.00395
Abstract: The mechanistic target of rapamycin (mTOR), via its two distinct multiprotein complexes, mTORC1, and mTORC2, plays a central role in the regulation of cellular growth, metabolism, and migration. A dysregulation of the mTOR pathway has in turn been implicated in several pathological conditions including insulin resistance and cancer. Overactivation of mTORC1 and disruption of mTORC2 function have been reported to induce insulin resistance. On the other hand, aberrant mTORC1 and mTORC2 signaling via either genetic alterations or increased expression of proteins regulating mTOR and its downstream targets have contributed to cancer development. These underlined the attractiveness of mTOR as a therapeutic target to overcome both insulin resistance and cancer. This review summarizes the evidence supporting the notion of intermittent, low dose rapamycin for treating insulin resistance. It further highlights recent data on the continuous use of high dose rapamycin analogs and related second generation mTOR inhibitors for cancer eradication, for overcoming chemoresistance and for tumor stem cell suppression. Within these contexts, the potential challenges associated with the use of mTOR inhibitors are also discussed. © 2016 Ong, Wang, Dai, Tseng, Loo and Sethi.
Source Title: Frontiers in Pharmacology
URI: https://scholarbank.nus.edu.sg/handle/10635/174246
ISSN: 16639812
DOI: 10.3389/fphar.2016.00395
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