PMID- 21490404
OWN - NLM
STAT- MEDLINE
DCOM- 20110621
LR  - 20220330
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 121
IP  - 4
DP  - 2011 Apr
TI  - Next-generation mTOR inhibitors in clinical oncology: how pathway complexity 
      informs therapeutic strategy.
PG  - 1231-41
LID - 44145 [pii]
LID - 10.1172/JCI44145 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell 
      growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The 
      mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient 
      deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events 
      constitutively activate mTOR in cancers. Here we provide a brief overview of the 
      signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights 
      into therapeutic anticancer targets - both those that have been tried in the 
      clinic with limited success and those currently under clinical development - that 
      knowledge of these pathways gives us.
FAU - Wander, Seth A
AU  - Wander SA
AD  - Braman Family Breast Cancer Institute, Sylvester Comprehensive Cancer Center, 
      University of Miami Miller School of Medicine, Miami, Florida 33136, USA.
FAU - Hennessy, Bryan T
AU  - Hennessy BT
FAU - Slingerland, Joyce M
AU  - Slingerland JM
LA  - eng
GR  - R01 CA105118/CA/NCI NIH HHS/United States
GR  - 5-R01-CA-105118-04/CA/NCI 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 - 20110401
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Antineoplastic Agents)
RN  - 0 (CRTC1 protein, human)
RN  - 0 (CRTC2 protein, human)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Transcription Factors)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Antineoplastic Agents/therapeutic use
MH  - Clinical Trials as Topic
MH  - Female
MH  - Humans
MH  - Male
MH  - Neoplasms/*drug therapy/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Signal Transduction/drug effects
MH  - Sirolimus/analogs & derivatives/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Transcription Factors/antagonists & inhibitors/metabolism
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/metabolism
PMC - PMC3069769
EDAT- 2011/04/15 06:00
MHDA- 2011/06/22 06:00
PMCR- 2011/12/31
CRDT- 2011/04/15 06:00
PHST- 2011/04/15 06:00 [entrez]
PHST- 2011/04/15 06:00 [pubmed]
PHST- 2011/06/22 06:00 [medline]
PHST- 2011/12/31 00:00 [pmc-release]
AID - 44145 [pii]
AID - 10.1172/JCI44145 [doi]
PST - ppublish
SO  - J Clin Invest. 2011 Apr;121(4):1231-41. doi: 10.1172/JCI44145. Epub 2011 Apr 1.