Recent advances in targeting mTOR signaling pathway using small molecule inhibitors

Abstract

Targeted-based cancer therapy (TBCT) or personalized medicine is one of the main treatment modalities for cancer that has been developed to decrease the undesirable effects of chemotherapy. Targeted therapy inhibits the growth of tumor cells by interrupting with particular molecules required for tumorigenesis and proliferation of tumor cells rather than interfering with dividing normal cells. Therefore, targeted therapies are anticipated to be more efficient than former tumor treatment agents with minimal side effects on non-tumor cells. Small molecule inhibitors (SMIs) are currently one of the most investigated anti-tumor agents of TBCT. These small organic agents target several vital molecules involved in cell biological processes and induce target cells apoptosis and necrosis. Mechanistic (mammalian) target of rapamycin (mTOR) complexes (mTORC1/2) control different intracellular processes, including growth, proliferation, angiogenesis and metabolism. Signaling pathways, in which mTOR complexes are involved in are usually dysregulated in various tumors and have been shown to be ideal targets for SMIs. Currently, different mTOR-SMIs are in the clinic for the treatment of cancer patients, and several others are in preclinical or clinical settings. In this review, we summarize recent advances in developing different mTOR inhibitors, which are currently in preclinical and clinical investigations or have been approved for cancer treatment.

Keywords: mTOR; signaling molecules; small-molecule inhibitor; targeted-based cancer therapy.