title: mTOR inhibitors in advanced renal cell carcinoma.
abstract: Better understanding of the molecular biology of renal cell carcinoma (RCC) has led to the development of several targeted anti-cancer agents, several of which have since received approval for treatment of advanced disease. Two of these, the intravenous agent temsirolimus and the oral everolimus, exhibit antitumor effects through inhibition of the mammalian target of rapamycin (mTOR) pathway. This article reviews their mechanisms of action in the context of the current understanding of RCC pathophysiology, the clinical data leading to their approval, class-specific toxicities, potential molecular mechanisms behind treatment resistance and novel treatment approaches for RCC that incorporate mTOR blockade.
authors.affiliation: Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 353 East 68th Street, New York, NY 10065, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Voss
authors.forename: Ana M
authors.initials: AM
authors.lastname: Molina
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
mesh_terms: D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism; D002986:Clinical Trials as Topic; D000068338:Everolimus; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus