PMID- 15578919
OWN - NLM
STAT- MEDLINE
DCOM- 20050210
LR  - 20211203
IS  - 1568-0096 (Print)
IS  - 1568-0096 (Linking)
VI  - 4
IP  - 8
DP  - 2004 Dec
TI  - Mammalian target of rapamycin (mTOR) inhibitors as anti-cancer agents.
PG  - 621-35
AB  - Highly specific signal transduction inhibitors are being developed as anti-cancer 
      agents against an array of molecular targets, with the promise of increased 
      selectivity and lower toxicity than classic cytotoxic chemotherapy agents. 
      Rapamycin and its analogues are a promising class of novel therapeutics that 
      specifically inhibit signaling from the serine-threonine kinase, mammalian target 
      of rapamycin (mTOR). mTOR is a key intermediary in multiple mitogenic signaling 
      pathways and plays a central role in modulating proliferation and angiogenesis in 
      normal tissues and neoplastic processes. Rapamycin potently inhibits T-cell 
      proliferation, and is approved for clinical use as an immuno-suppressant 
      following kidney transplantation. Hyperactivation of mTOR signaling has been 
      implicated in tumorigenesis, and promising pre-clinical studies in several tumor 
      types suggest that the anti-proliferative and anti-angiogenic properties of 
      rapamycin may be useful in cancer therapy. These studies have led to several 
      clinical trials evaluating the safety and efficacy of rapamycin analogs in cancer 
      therapy. The goal of this article is to review the mechanism of action of 
      rapamycin as an anti-cancer agent, and to review the clinical experience with 
      rapamycin and rapamycin analogs as immunosuppressive and anti-neoplastic 
      therapeutic agents.
FAU - Rao, Ravi D
AU  - Rao RD
AD  - Department of Oncology, Mayo Clinic College of Medicine, 200 First St. SW, 
      Rochester, MN 55905, USA.
FAU - Buckner, Jan C
AU  - Buckner JC
FAU - Sarkaria, Jann N
AU  - Sarkaria JN
LA  - eng
GR  - K08-CA80829/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - Netherlands
TA  - Curr Cancer Drug Targets
JT  - Current cancer drug targets
JID - 101094211
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.- (Protein Kinases)
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  - Animals
MH  - Antineoplastic Agents/*therapeutic use
MH  - Humans
MH  - Neoplasms/*drug therapy/metabolism/pathology
MH  - Protein Kinase Inhibitors/therapeutic use
MH  - Protein Kinases/*metabolism
MH  - Sirolimus/analogs & derivatives/*therapeutic use
MH  - TOR Serine-Threonine Kinases
RF  - 89
EDAT- 2004/12/08 09:00
MHDA- 2005/02/11 09:00
CRDT- 2004/12/08 09:00
PHST- 2004/12/08 09:00 [pubmed]
PHST- 2005/02/11 09:00 [medline]
PHST- 2004/12/08 09:00 [entrez]
AID - 10.2174/1568009043332718 [doi]
PST - ppublish
SO  - Curr Cancer Drug Targets. 2004 Dec;4(8):621-35. doi: 10.2174/1568009043332718.