PMID- 23408390
OWN - NLM
STAT- MEDLINE
DCOM- 20140116
LR  - 20220408
IS  - 1527-3350 (Electronic)
IS  - 0270-9139 (Print)
IS  - 0270-9139 (Linking)
VI  - 58
IP  - 2
DP  - 2013 Aug
TI  - The mTOR pathway in hepatic malignancies.
PG  - 810-8
LID - 10.1002/hep.26323 [doi]
AB  - The mechanistic/mammalian target of rapamycin (mTOR) pathway plays a critical 
      role in cellular metabolism, growth, and proliferation and has been evaluated as 
      a target for therapy in various malignancies. The mTOR pathway is a major 
      tumor-initiating pathway in hepatocellular carcinoma, with up-regulation seen in 
      up to 50% of tumors. Metformin, which represses mTOR signaling by activating 
      adenosine monophosphate-activated protein kinase, has been shown to decrease 
      liver carcinogenesis in population studies. mTOR inhibitors such as everolimus 
      have been evaluated as adjunctive chemotherapy with some success, although 
      efficacy has been limited by the lack of complete mTOR pathway inhibition. The 
      active site mTOR inhibitors hold greater promise, given that they offer complete 
      mTOR suppression. There is also evidence of mTOR pathway activation in 
      cholangiocarcinoma, although its biological significance in initiating and 
      promoting tumor progression remains ambiguous. This review provides an overview 
      of the complex biochemistry behind the mTOR pathway and its role in 
      carcinogenesis, especially as it pertains to hepatic malignancies.
CI  - Copyright (c) 2013 American Association for the Study of Liver Diseases.
FAU - Bhat, Mamatha
AU  - Bhat M
AD  - Division of Gastroenterology, McGill University Health Centre, Montreal, Canada.
FAU - Sonenberg, Nahum
AU  - Sonenberg N
FAU - Gores, Gregory J
AU  - Gores GJ
LA  - eng
GR  - R01 DK041876/DK/NIDDK NIH HHS/United States
GR  - R37 DK041876/DK/NIDDK NIH HHS/United States
GR  - DK41876/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20130417
PL  - United States
TA  - Hepatology
JT  - Hepatology (Baltimore, Md.)
JID - 8302946
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Bile Duct Neoplasms/physiopathology
MH  - Bile Ducts, Intrahepatic
MH  - Carcinoma, Hepatocellular/physiopathology
MH  - Cholangiocarcinoma/physiopathology
MH  - Disease Models, Animal
MH  - Humans
MH  - Liver Neoplasms/*physiopathology
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/*physiology
PMC - PMC3688698
MID - NIHMS447067
EDAT- 2013/02/15 06:00
MHDA- 2014/01/17 06:00
PMCR- 2014/08/01
CRDT- 2013/02/15 06:00
PHST- 2012/12/18 00:00 [received]
PHST- 2013/02/07 00:00 [accepted]
PHST- 2013/02/15 06:00 [entrez]
PHST- 2013/02/15 06:00 [pubmed]
PHST- 2014/01/17 06:00 [medline]
PHST- 2014/08/01 00:00 [pmc-release]
AID - 10.1002/hep.26323 [doi]
PST - ppublish
SO  - Hepatology. 2013 Aug;58(2):810-8. doi: 10.1002/hep.26323. Epub 2013 Apr 17.