Copyright ©2012 Baishideng. All rights reserved.
World J Transplant. Oct 24, 2012; 2(5): 74-83
Published online Oct 24, 2012. doi: 10.5500/wjt.v2.i5.74
Antineoplastic effects of mammalian target of rapamycine inhibitors
Maurizio Salvadori
Maurizio Salvadori, Renal Unit, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Italy
Author contributions: Salvadori M solely contributed to this paper.
Correspondence to: Maurizio Salvadori, MD, Professor, Renal Unit, Careggi University Hospital, Viale Pieraccini 18, Florence 50139, Italy.
Telephone: +39-55-7949269 Fax: +39-55-435878
Received: July 14, 2011
Revised: August 8, 2012
Accepted: October 20, 2012
Published online: October 24, 2012

Cancer after transplantation is the third cause of death and one of the more relevant comorbidities. Aim of this review is to verify the role of different pathogenetic mechanisms in cancer development in transplant patients and in general population as well. In particular has been outlined the different role exerted by two different families of drug as calcineurin inhibitor and mammalian target of rapamycin (mTOR) inhibitor. The role of mTOR pathways in cell homeostasis is complex but enough clear. As a consequence the mTOR pathway deregulation is involved in the genesis of several cancers. Hence the relevant role of mTOR inhibitors. The authors review the complex mechanism of action of mTOR inhibitors, not only for what concerns the immune system but also other cells as endothelial, smooth muscle and epithelial cells. The mechanism of action is still now not completely defined and understood. It implies the inhibition of mTOR pathway at different levels, but mainly at level of the phosphorylation of several intracellular kinases that contribute to activate mTOR complex. Many prospective and retrospective studies in transplant patients document the antineoplastic role of mTOR inhibition. More recently mTOR inhibitors proven to be effective in the treatment of some cancers also in general population. Kidney cancers, neuroendocrine tumors and liver cancers seem to be the most sensitive to these drugs. Best results are obtained with a combination treatment, targeting the mTOR pathway at different levels.

Keywords: Transplant patients, Cancer treatment, Cell proliferation, Mammalian target of rapamycin inhibition, Mammalian target of rapamycin pathway, Protooncogenes, Tumor suppressors