Targeting the mammalian target of rapamycin (mTOR): a new approach to treating cancer.
mTOR is a downstream mediator in the PI3K/Akt signalling pathway, which plays a critical role in regulating basic cellular functions. These include cell proliferation, survival, mobility and angiogenesis. Rapamycin and its analogues (CCI-779, RAD001 and AP23573) have specific antagonistic action on the function of mTOR. This leads to inhibition of the downstream signalling elements and results in the cell cycle arrest in the G1 phase. This group of drugs may have a place in Oncology for the treatment of cancers, which occur as a result of increased activity of the PI3 kinase/Akt/m-TOR pathway. The basic structure of the pathway was reviewed in this article, together with results of the clinical studies targeting mTOR for cancer therapy. This is an exciting area for development and poses many challenges to researchers.
Chan
S
S
The City Hospital, Nottingham NG5 1PB, UK. schan2@ncht.trent.nhs.uk
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus