mTOR inhibitors in the treatment of cancer

Background: The mammalian target of rapamycin (mTOR) is a protein kinase of the phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway with a central role in the control of cell proliferation, survival, mobility and angiogenesis. Dysregulation of mTOR pathway has been found in many human tumours; therefore, the mTOR pathway is considered an important target for the development of new anticancer drugs. Objective: To review the mTOR pathway, the role of the mTOR inhibitors in cancer treatment, the preclinical features and clinical results of the three mTOR inhibitors currently in development, temsirolimus, everolimus and deforolimus. Methods: Review of the published literature (abstracts, full papers) since 1995 on mTOR pathway and related pathway signalling, rapamycin and analogues. Results/conclusion: With each of the three mTOR inhibitors temsirolimus (CCI-779), everolimus (RAD001) and deforolimus (AP23573), a safe schedule of treatment has been defined and promising results of antitumour activity have been achieved in a variety of solid tumours, thus confirming the preclinical expectations.