Abstract:
mTOR is a very important kinase which plays a central role in regulating cell metabolism, growth, and proliferation. Interfering or inhibiting mTOR activity would stop cell growth and subsequently, death in normal cells, especially in cancer cells. Therefore, mTOR has been considered as a critical potential target for cancer therapy. Subsequently, a series of mTOR inhibitors have already been invented and tested in clinics. However, an anti-tumor effect was not indicated as expected. Therefore, it was thought that some factors blocking the mTOR pathway and considerably weakening the clinical efficacy of its inhibitors must be in existence. After intensive studies, feedback mechanisms of mTOR signaling pathway were identified. Simultaneously, the inhibition of mTOR has been observed to activate multi pathways related to cell growth and proliferation. Thus, the feedback mechanisms were regarded as the direct reasons that attenuated the efficacy of mTOR inhibitors and resulted in unsatisfactory clinical effects. In the present paper, the feedback-activated pathways of mTOR-AKT, mTOR-ERK, and mTOR-eIF4E will be discussed in detail, as well as other strategies that rapamycin analogs and specified pathway inhibitors can be combined to treat cancer. The present paper is aimed to fully discuss the potential antitumor activity of mTOR inhibitors.