[Antitumoral effect of proliferation signal inhibitors].
The mammalian target of rapamycin (mTOR) is implicated in cell growth especially during cancer development and progression. Its action is dependent on well known oncogenic pathways that regulate tumor cell growth and cell cycle progression, in response to different stimuli. Sirolimus, temsirolimus and everolimus are specific inhibitors of mTOR that have originally been characterized by their antifungal and immunosuppressive properties, but also significantly inhibit cancer cells'proliferation, invasion, and metastasis, and promote apoptosis. In addition, mTOR inhibitors display potent antiangiogenic properties by the suppression of vascular endothelial growth factor signal transduction. The antitumoral effects of mTOR inhibitors, as a monotherapy or in combination with tyrosine kinase inhibitors or usual cytotoxic agents, have been extensively suggested in preclinical studies, including animal models. In a clinical setting, preliminary reports have demonstrated that mTOR inhibitors use is associated with an acceptable safety profile. Currently, mTOR inhibitors are tested in multiple trials and various cancer types, usually in intermittent schedules to avoid significant immunosuppression. Of particular interest is the use of mTOR inhibitors in the field of organ transplantation, including liver transplantation, in preventive or curative strategies, for the treatment of recurrent hepatocellular carcinoma and de novo post-transplantation malignancies.
Dumortier
J
J
Unité de transplantation hépatique, Hôpital Edouard Herriot, pavillon H bis, Lyon, France. jerome.dumortier@chu-lyon.fr
D020533:Angiogenesis Inhibitors; D000818:Animals; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D016031:Liver Transplantation; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000517:prevention & control; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus