Mammalian target of rapamycin is a promising target for novel therapeutic strategy against cancer.
Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (P13K) pathway. The P13K/Akt signaling pathway plays a critical role in regulating basic cellular functions such as control of transcription and translation. mTOR is a downstream mediator of P13K/Akt and, as a result of its position, it has a central role in controlling cellular growth and division. Previous reports demonstrated that rapamycin, which inhibits mTOR activity, sensitizes certain resistant cancer cells to chemotherapeutic agents. These facts have made mTOR to be viewed as an important target for anti-cancer therapeutics development. Evidence suggests that the rapamycin derivatives CCI-779 and RAD001 could induce G1-S cell cycle delay and eventually apoptosis, depending on inner cellular characteristics of tumor cells. At present, CCI-779 and RAD001 are being evaluated in cancer clinical trials. From recent studies, these drugs appear to have a safe toxicity profile with skin rashes and mucositis being prominent and dose-limiting. In this review we discuss about the principal mechanisms of mTOR action and the current place of mTOR inhibitors as novel therapeutic agents against cancer.
Bjelogrlić
S K
SK
Department of Experimental Pharmacology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia. zanab@bitsyu.net
Srdić
T
T
Radulović
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D000970:Antineoplastic Agents; D000068338:Everolimus; D007166:Immunosuppressive Agents; D019869:Phosphatidylinositol 3-Kinases; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; C401859:temsirolimus; C546842:MTOR protein, human