PMID- 21547705
OWN - NLM
STAT- MEDLINE
DCOM- 20111031
LR  - 20220408
IS  - 1776-260X (Electronic)
IS  - 1776-2596 (Linking)
VI  - 6
IP  - 1
DP  - 2011 Mar
TI  - Mechanisms of mTOR inhibitor resistance in cancer therapy.
PG  - 17-27
LID - 10.1007/s11523-011-0167-8 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that 
      regulates cell cycle progression, protein translation, metabolism, and cellular 
      proliferation. The mTOR pathway promotes cell proliferation under energy or 
      nutrient-rich conditions by increasing ribosomal biogenesis and protein 
      synthesis. Since enhanced activity of the mTOR pathway is frequently observed in 
      malignant cells, inhibition of this kinase has become an attractive strategy to 
      treat cancer. Rapamycin and its analogs temsirolimus, everolimus, and 
      ridaforolimus referred to as "rapalogs" have demonstrated promising efficacy 
      against renal cell carcinoma and are under investigation for the treatment of 
      other malignancies. However, the emergence of drug resistance may ultimately 
      limit the utility of rapalog therapy. Here we summarize the known mechanisms of 
      resistance to mTOR-inhibitor therapy and describe potential strategies to 
      overcome these for the current agents that target this pathway.
FAU - Carew, Jennifer S
AU  - Carew JS
AD  - Department of Medicine and Institute for Drug Development, Cancer Therapy and 
      Research Center at The University of Texas Health Science Center, 14960 Omicron 
      Drive, San Antonio, TX 78245, USA.
FAU - Kelly, Kevin R
AU  - Kelly KR
FAU - Nawrocki, Steffan T
AU  - Nawrocki ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20110309
PL  - France
TA  - Target Oncol
JT  - Targeted oncology
JID - 101270595
RN  - 0 (Antibiotics, Antineoplastic)
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/*therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Humans
MH  - Molecular Targeted Therapy
MH  - Neoplasms/*drug therapy
MH  - Sirolimus/*analogs & derivatives/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
EDAT- 2011/05/07 06:00
MHDA- 2011/11/01 06:00
CRDT- 2011/05/07 06:00
PHST- 2011/01/20 00:00 [received]
PHST- 2011/02/22 00:00 [accepted]
PHST- 2011/05/07 06:00 [entrez]
PHST- 2011/05/07 06:00 [pubmed]
PHST- 2011/11/01 06:00 [medline]
AID - 10.1007/s11523-011-0167-8 [doi]
PST - ppublish
SO  - Target Oncol. 2011 Mar;6(1):17-27. doi: 10.1007/s11523-011-0167-8. Epub 2011 Mar 
      9.