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.