Everolimus.
Everolimus, an orally administered rapamycin analog, has recently been approved by the U.S. Food and Drug Administration for treatment of renal cell carcinoma (RCC) refractory to inhibitors of vascular endothelial growth factor (VEGF) receptor signaling. Everolimus significantly increased progression-free survival (median PFS for the everolimus treated group was 4.0 months versus 1.9 months for the placebo group), although tumor regressions were observed only infrequently. Although the target for everolimus, [the serine-threonine kinase mammalian target of rapamycin (mTOR)] is well established, the mechanism by which this agent retards tumor growth is not well defined. Further, biomarkers that predict tumor sensitivity are still elusive. The mechanism of action, preclinical antitumor activity, and clinical activity of everolimus against RCC are reviewed.
Houghton
Peter J
PJ
Center for Childhood Cancer, The Research Institute, Nationwide Children's Hospital, Columbus, Ohio 43205, USA. Peter.Houghton@nationwidechildrens.org
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D000068338:Everolimus; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology
D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus