Antineoplastic effects of mammalian target of rapamycine inhibitors  

作　　者：Maurizio Salvadori 

机构地区：[1]Renal Unit,Careggi University Hospital

出　　处：《World Journal of Transplantation》2012年第5期74-83,共10页世界移植杂志

摘　　要：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(m TOR) inhibitor. The role of m TOR pathways in cell homeostasis is complex but enough clear. As a consequence the m TOR pathway deregulation is involved in the genesis of several cancers. Hence the relevant role of m TOR inhibitors. The authors review the complex mechanism of action of m TOR 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 m TOR pathway at different levels, but mainly at level of the phosphorylation of several intracellular kinases that contribute to activate m TOR complex. Many prospective and retrospective studies in transplant patients document the antineoplastic role of m TOR inhibition. More recently m TOR 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 m TOR pathway at different levels.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(m TOR) inhibitor. The role of m TOR pathways in cell homeostasis is complex but enough clear. As a consequence the m TOR pathway deregulation is involved in the genesis of several cancers. Hence the relevant role of m TOR inhibitors. The authors review the complex mechanism of action of m TOR 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 m TOR pathway at different levels, but mainly at level of the phosphorylation of several intracellular kinases that contribute to activate m TOR complex. Many prospective and retrospective studies in transplant patients document the antineoplastic role of m TOR inhibition. More recently m TOR 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 m TOR pathway at different levels.

关 键 词：Transplant patients Cancer treatment Cell proliferation MAMMALIAN TARGET of RAPAMYCIN inhibition MAMMALIAN TARGET of RAPAMYCIN pathway PROTOONCOGENES Tumor SUPPRESSORS 

分 类 号：R[医药卫生]