PMID- 20591820
OWN - NLM
STAT- MEDLINE
DCOM- 20110502
LR  - 20211203
IS  - 1569-8041 (Electronic)
IS  - 0923-7534 (Linking)
VI  - 22
IP  - 2
DP  - 2011 Feb
TI  - Updating progress in sarcoma therapy with mTOR inhibitors.
PG  - 280-7
LID - 10.1093/annonc/mdq307 [doi]
AB  - BACKGROUND: Sarcomas are a diverse group of difficult-to-treat connective tissue 
      neoplasms. The mammalian target of rapamycin (mTOR) pathway has been identified 
      as a therapeutic target in many sarcomas and this article reviews the role of 
      this pathway and updates clinical data for the available mTOR inhibitors. DESIGN: 
      Reference sources were selected by the author for searches in PubMed and EMBASE, 
      with search terms dependent on the particular subtopic. RESULTS: mTOR is a 
      protein kinase that regulates cell growth and proliferation and is abnormally 
      activated in many human tumours. Several disruptions of phosphatidylinositol-3' 
      kinase (PI3K)-Akt signalling are associated with different sarcoma types. The 
      macrolide antibiotic rapamycin and synthetic derivatives sirolimus, temsirolimus, 
      everolimus and ridaforolimus have been investigated in several tumour types and 
      their potential for the treatment of sarcoma is being explored, with varying 
      degrees of success. The PI3K-Akt-mTOR pathway is also implicated in resistance 
      mechanisms to antineoplastic therapies, and mTOR inhibitors therefore have the 
      potential to restore sensitivity to patients with treatment-resistant disease. 
      CONCLUSIONS: The PI3K-Akt-mTOR pathway is an exciting target for therapy in many 
      types of solid malignancies and its blockade represents an opportunity to improve 
      outcomes in poor-prognosis sarcoma.
FAU - Blay, J-Y
AU  - Blay JY
AD  - Department of Medical Oncology, Centre Leon Berard, Lyon, France. 
      BLAY@lyon.fnclcc.fr
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20100629
PL  - England
TA  - Ann Oncol
JT  - Annals of oncology : official journal of the European Society for Medical 
      Oncology
JID - 9007735
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Cell Division
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Sarcoma/*drug therapy/pathology
MH  - Signal Transduction
MH  - Soft Tissue Neoplasms/*drug therapy/pathology
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
EDAT- 2010/07/02 06:00
MHDA- 2011/05/03 06:00
CRDT- 2010/07/02 06:00
PHST- 2010/07/02 06:00 [entrez]
PHST- 2010/07/02 06:00 [pubmed]
PHST- 2011/05/03 06:00 [medline]
AID - S0923-7534(19)38645-4 [pii]
AID - 10.1093/annonc/mdq307 [doi]
PST - ppublish
SO  - Ann Oncol. 2011 Feb;22(2):280-7. doi: 10.1093/annonc/mdq307. Epub 2010 Jun 29.