Targeting the molecular target of rapamycin (mTOR)

PURPOSE OF REVIEW: The molecular target of rapamycin, which is a member of the phosphoinositide 3-kinase related kinase family and a central modulator of cell growth, is a unique and prime strategic target for anticancer therapeutic development. RECENT FINDINGS: The molecular target of rapamycin plays a critical role in transducing proliferative signals mediated through the phosphatidylinositol 3 kinase and protein kinase B signaling pathways, principally by activating downstream protein kinases that are required for both ribosomal biosynthesis and translation of mRNAs of proteins that are essential for G1 to S phase traverse. By targeting the molecular target of rapamycin with high potency and specificity, the immunosuppressant and antiproliferative agent rapamycin inhibits signals required for cell cycle progression, cell growth, and proliferation. Both rapamycin and several rapamycin analogs with more favorable pharmaceutical properties have demonstrated impressive growth inhibitory effects against a broad range of human cancers in both preclinical and early clinical evaluations. SUMMARY: This review discusses recent findings regarding the principal mechanisms of action of the rapamycins, the potential utility of these agents as anticancer therapeutics, clinical results to date, and developmental challenges that lie ahead.