PMID- 16305491
OWN - NLM
STAT- MEDLINE
DCOM- 20060201
LR  - 20211203
IS  - 1566-5240 (Print)
IS  - 1566-5240 (Linking)
VI  - 5
IP  - 7
DP  - 2005 Nov
TI  - Mammalian target of rapamycin as a therapeutic target in leukemia.
PG  - 653-61
AB  - Reflecting its critical role in integrating cell growth and division with the 
      cellular nutritional environment, the mammalian target of rapamycin *(mTOR) is a 
      highly conserved downstream effector of the phosphatidylinositol 3-kinase 
      (PI3K)/Akt (protein kinase B) signaling pathway. mTOR activates both the 40S 
      ribosomal protein S6 kinase (p70s6k) and the eukaryotic initiation factor 
      4E-binding protein-1. As a consequence of inhibiting its downstream messengers, 
      mTOR inhibitors prevent cyclin-dependent kinase (CDK) activation, inhibit 
      retinoblastoma protein phosphorylation, and accelerate the turnover of cyclin D1, 
      leading to a deficiency of active CDK4/cyclin D1 complexes, all of which may help 
      cause GI phase arrest. Constitutive activation of the PI3K/Akt kinases occur in 
      human leukemias. FLT3, VEGF, and BCR-ABL mediate their activities via mTOR. New 
      rapamycin analogs including CCI-779, RAD001, and AP23573, are entering clinical 
      studies for patients with hematologic malignancies.
FAU - Giles, Francis J
AU  - Giles FJ
AD  - Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 
      Houston, TX 77030, USA. fgiles@mdanderson.org
FAU - Albitar, Maher
AU  - Albitar M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - Netherlands
TA  - Curr Mol Med
JT  - Current molecular medicine
JID - 101093076
RN  - 624KN6GM2T (temsirolimus)
RN  - 9HW64Q8G6G (Everolimus)
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  - Everolimus
MH  - Hematologic Neoplasms/metabolism
MH  - Humans
MH  - Leukemia/*drug therapy/*metabolism
MH  - Protein Kinases/chemistry/genetics/*metabolism
MH  - Sirolimus/analogs & derivatives/pharmacology/therapeutic use
MH  - Substrate Specificity
MH  - TOR Serine-Threonine Kinases
RF  - 151
EDAT- 2005/11/25 09:00
MHDA- 2006/02/02 09:00
CRDT- 2005/11/25 09:00
PHST- 2005/11/25 09:00 [pubmed]
PHST- 2006/02/02 09:00 [medline]
PHST- 2005/11/25 09:00 [entrez]
AID - 10.2174/156652405774641034 [doi]
PST - ppublish
SO  - Curr Mol Med. 2005 Nov;5(7):653-61. doi: 10.2174/156652405774641034.