Mechanisms of Disease: survival benefit of temsirolimus validates a role for mTOR in the management of advanced RCC.
Temsirolimus is a specific inhibitor of mammalian target of rapamycin (mTOR) that is approved for the treatment of advanced renal cell carcinoma. mTOR is unique among antitumor drug targets because it is a convergence point for many signaling pathways. Activation of mTOR by various growth signals increases the synthesis of proteins needed for cell-cycle progression and tumor growth. Temsirolimus demonstrates a significant improvement in overall survival in patients with advanced renal cell carcinoma and poor-prognostic features, thereby validating the importance of mTOR in the natural history of this disease. mTOR might also be an important target in other tumor types, and more than 100 ongoing clinical trials are designed to identify additional malignancies that respond to temsirolimus and other mTOR inhibitors, either alone or in combination with other targeted agents or chemotherapy.
Figlin
Robert A
RA
Division of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Care Center, Duarte, CA 91010, USA. rfiglin@coh.org
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016019:Survival Analysis
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D020123:Sirolimus