PMID- 19694499
OWN - NLM
STAT- MEDLINE
DCOM- 20091124
LR  - 20231105
IS  - 1744-7631 (Electronic)
IS  - 1472-8222 (Print)
IS  - 1472-8222 (Linking)
VI  - 13
IP  - 10
DP  - 2009 Oct
TI  - Enhancing mTOR-targeted cancer therapy.
PG  - 1193-203
LID - 10.1517/14728220903225008 [doi]
AB  - BACKGROUND: The mammalian target of rapamycin (mTOR) has emerged as an attractive 
      cancer therapeutic target. Accordingly, several mTOR inhibitors (e.g., rapamycin 
      and its analogs; rapalogs) are currently being tested in many cancer clinical 
      trials. Despite the encouraging results showing that some rapalogs improved 
      overall survival among patients with metastatic renal-cell carcinoma, the 
      single-agent activity of rapalogs in most other tumor-types has been modest, at 
      best. OBJECTIVE: To review the current understanding of the mTOR axis and discuss 
      potential strategies to enhance mTOR-targeted cancer therapy. METHODS: 
      Preclinical and clinical data in peer-reviewed reports on the novel biological 
      and therapeutic parts of the mTOR axis are discussed. CONCLUSION: The mTOR axis 
      involves complex regulatory networks. Inhibition of the mTOR axis with a rapalog 
      induces feedback activation of several survival signaling pathways such as Akt 
      activation, which, in turn, blunt rapalogs' anticancer efficacy. Thus, blockage 
      or prevention of the activation of these survival signaling pathways may enhance 
      mTOR-targeted cancer therapy.
FAU - Wang, Xuerong
AU  - Wang X
AD  - Emory University School of Medicine, Winship Cancer Institute, Department of 
      Hematology, Atlanta, GA 30322, USA.
FAU - Sun, Shi-Yong
AU  - Sun SY
LA  - eng
GR  - P01 CA116676-01/CA/NCI NIH HHS/United States
GR  - R01 CA118450-04/CA/NCI NIH HHS/United States
GR  - R01 CA118450-01/CA/NCI NIH HHS/United States
GR  - P01 CA116676-040001/CA/NCI NIH HHS/United States
GR  - P01 CA116676/CA/NCI NIH HHS/United States
GR  - R01 CA118450/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Review
PL  - England
TA  - Expert Opin Ther Targets
JT  - Expert opinion on therapeutic targets
JID - 101127833
RN  - 0 (Antineoplastic 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)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Humans
MH  - Neoplasms/*drug therapy
MH  - Protein Kinases/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
PMC - PMC2810099
MID - NIHMS164089
EDAT- 2009/08/22 09:00
MHDA- 2009/12/16 06:00
PMCR- 2010/10/01
CRDT- 2009/08/22 09:00
PHST- 2009/08/22 09:00 [entrez]
PHST- 2009/08/22 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 10.1517/14728220903225008 [doi]
PST - ppublish
SO  - Expert Opin Ther Targets. 2009 Oct;13(10):1193-203. doi: 
      10.1517/14728220903225008.