The mammalian target of rapamycin (mTOR) is a downstream effector of the phosphatidylinositol 3-kinase (PI3K)/Akt (protein kinase B) signaling pathway that mediates cell survival and proliferation. It is increasingly apparent that mTOR signaling impacts most major cellular functions. Because mTOR deregulation occurs in human disease, including cancer, obesity, type 2 diabetes, and neurodegeneration, there are significant ongoing efforts to pharmacologically target the mTOR pathway (1). Treatment with polyphenols in various prostate cancer cell lines showed a decrease in the mTOR levels as detected by anti- mTOR antibodies leading to a decrease in cell proliferation and cell death (2). Available data suggests that mTOR is a central modulator of cell growth, is a prime strategic target for anti-cancer therapeutic development.
mTOR plays a critical role in transducing proliferative signals mediated through the PI3K/protein kinase B (Akt) signaling pathway, principally by activating downstream protein kinases that are required for both ribosomal biosynthesis and translation of key mRNAs of proteins required for G(1) to S phase traverse. By targeting mTOR, the immunsuppressant and antiproliferative agent rapamycin inhibits signals required for cell cycle progression, cell growth, and proliferation (3). The evidence linking activated mTOR signaling to various cancers and other diseases has generated significant interest in targeting the pathway for therapy and many rapamycin analogs are now being tested in clinic.
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