PMID- 16258427
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20211203
IS  - 1543-0790 (Print)
IS  - 1543-0790 (Linking)
VI  - 1
IP  - 7
DP  - 2003 Jul
TI  - mTOR inhibitors in hematologic malignancies.
PG  - 419-23
AB  - Most hematologic malignancies are characterized by initial responsiveness to 
      chemotherapeutic regimens, but many patients still die from their disease. Among 
      the agents currently in clinical development, there is a strong rationale for 
      evaluating rapamycin derivatives. Rapamycin was originally developed as an 
      immunosuppressant and is approved by the US Food and Drug Administration for the 
      treatment of kidney allograft transplant rejection. Two related compounds, RAD001 
      and CCI-779, are under development as cancer therapeutics. Rapamcyin binds to the 
      immunophilin FK506-binding protein 12 and this protein/drug complex binds to and 
      inhibits the activity of the mammalian target of rapamycin (mTOR). Among its many 
      functions, mTOR regulates the translation of a specific subset of mRNA 
      transcripts that encode for proteins involved in regulating the G1 to S phase 
      transition. This review focuses on recent advances in the understanding of the 
      mechanisms of cell growth inhibition by rapamycin, clinical trial results for the 
      2 agents being developed as cancer agents, and the rationale supporting the 
      evaluation of this class of agent in hematological malignancies.
FAU - Dancey, Janet E
AU  - Dancey JE
AD  - Investigational Drug Branch, Cancer Treatment Evaluation Program, Division of 
      Cancer Treatment and Diagnosis, National Cancer Institute, 6130 Executive 
      Boulevard, Rockville, MD 20854, USA. danceyj@ctep.nci.nih.gov
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Clin Adv Hematol Oncol
JT  - Clinical advances in hematology & oncology : H&O
JID - 101167661
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Immunosuppressive Agents)
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  - Cell Cycle/drug effects
MH  - Clinical Trials as Topic
MH  - Enzyme Inhibitors/therapeutic use
MH  - Hematologic Neoplasms/drug therapy
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology/*therapeutic use
MH  - Protein Kinases/*physiology
MH  - Sirolimus/pharmacology/*therapeutic use
MH  - TOR Serine-Threonine Kinases
RF  - 74
EDAT- 2005/11/01 09:00
MHDA- 2005/11/16 09:00
CRDT- 2005/11/01 09:00
PHST- 2005/11/01 09:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2005/11/01 09:00 [entrez]
PST - ppublish
SO  - Clin Adv Hematol Oncol. 2003 Jul;1(7):419-23.