PMID- 16916489
OWN - NLM
STAT- MEDLINE
DCOM- 20061102
LR  - 20220801
IS  - 1527-2729 (Print)
IS  - 1534-6277 (Linking)
VI  - 7
IP  - 4
DP  - 2006 Jul
TI  - Inhibition of the phosphatidylinositol 3-kinase/mammalian target of rapamycin 
      pathway in hematologic malignancies.
PG  - 285-94
AB  - The phosphatidylinositol 3-kinase (PI3-K)/mammalian target of rapamycin (mTOR) 
      signal transduction pathway integrates signals from multiple receptor tyrosine 
      kinases to control cell proliferation and survival. Key components of the pathway 
      are the lipid kinase PI3-K, the small guanosine triphosphate-binding protein 
      Rheb, and the protein kinases Akt and mTOR. Important natural inhibitors of the 
      pathway include the lipid phosphatase PTEN and the tuberous sclerosis complex. 
      Several components of this pathway are targeted by investigational antineoplastic 
      agents. Rapamycin (sirolimus), the prototypic mTOR inhibitor, exhibits activity 
      in acute myeloid leukemia. Three rapamycin analogs, temsirolimus, everolimus, and 
      AP23573, are in clinical trials for various hematologic malignancies. 
      Temsirolimus has produced a 38% overall response rate in relapsed mantle cell 
      lymphoma, and AP23573 has demonstrated activity in acute leukemia. Everolimus is 
      undergoing clinical testing in lymphoma (Hodgkin and non-Hodgkin) and multiple 
      myeloma. In addition, perifosine, an inhibitor of Akt activation that exhibits 
      substantial antimyeloma activity in preclinical models, is being examined in 
      relapsed multiple myeloma. Based on results obtained to date, it appears that 
      inhibitors of the PI3-K/mTOR pathway hold promise as single agents and in 
      combination for hematologic malignancies.
FAU - Witzig, Thomas E
AU  - Witzig TE
AD  - Mayo Clinic, Stabile 628, 200 First Street SW, Rochester, MN 55905, USA. 
      witzig@mayo.edu
FAU - Kaufmann, Scott H
AU  - Kaufmann SH
LA  - eng
GR  - CA97274/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Curr Treat Options Oncol
JT  - Current treatment options in oncology
JID - 100900946
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Phosphoinositide-3 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  - Antibiotics, Antineoplastic/*pharmacology
MH  - Hematologic Neoplasms/*drug therapy/metabolism
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinases/*drug effects
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases
RF  - 59
EDAT- 2006/08/19 09:00
MHDA- 2006/11/03 09:00
CRDT- 2006/08/19 09:00
PHST- 2006/08/19 09:00 [pubmed]
PHST- 2006/11/03 09:00 [medline]
PHST- 2006/08/19 09:00 [entrez]
AID - 10.1007/s11864-006-0038-1 [doi]
PST - ppublish
SO  - Curr Treat Options Oncol. 2006 Jul;7(4):285-94. doi: 10.1007/s11864-006-0038-1.