mTOR pathway inhibition in renal cell carcinoma.
Renal cell carcinoma therapy has changed in a very significant way in the last few years. Up to 5 new agents have been developed, improving the results previously achieved with cytokine therapy. Bevacizumab, sorafenib, sunitinib, temsirolimus, and everolimus are now part of the therapeutic arsenal for this illness. Particularly, this has been the first tumoral type in which inhibition of mammalian target of rapamycin (mTOR) has proved its efficacy in phase III trials, either as first-line therapy for poor prognosis patients (temsirolimus, CCI-779) or as second-line therapy after failure of tyrosine-kinase inhibitors (everolimus, RAD001). In this paper, we review the basis for mTOR inhibition in RCC, and discuss the results of the trials involving temsirolimus and everolimus for the treatment of this disease.
Pinto Marín
Alvaro
A
Medical Oncology Department, University Hospital La Paz, Madrid, Spain. alvaro_pinto_marin@hotmail.com
Redondo Sánchez
Andrés
A
Espinosa Arranz
Enrique
E
Zamora Auñón
Pilar
P
Castelo Fernández
Beatriz
B
González Barón
Manuel
M
D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000201:enzymology*; D017326:Clinical Trials, Phase III as Topic; D000068338:Everolimus; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000201:enzymology*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction; D020123:Sirolimus / Q000031:analogs & derivatives / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016896:Treatment Outcome
D047428:Protein Kinase Inhibitors; C401859:temsirolimus; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus