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Targeted inhibition of mammalian target of rapamycin for the treatment of advanced renal cell carcinoma
Author(s) -
Kapoor Anil,
Figlin Robert A.
Publication year - 2009
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.24409
Subject(s) - temsirolimus , medicine , everolimus , sunitinib , sorafenib , renal cell carcinoma , sirolimus , pi3k/akt/mtor pathway , oncology , tyrosine kinase inhibitor , kidney cancer , discovery and development of mtor inhibitors , targeted therapy , clinical trial , cancer , cancer research , hepatocellular carcinoma , signal transduction , biology , biochemistry
Clinical trials have validated the importance of mammalian target of rapamycin (mTOR) as a targeted mechanism in the treatment of renal cell carcinoma (RCC). Temsirolimus, an mTOR inhibitor that is approved for treatment of advanced RCC, has demonstrated both overall survival benefits and progression‐free survival benefits versus interferon‒α as first‐line treatment for patients with poor prognostic features. Exploratory subset analyses indicated that temsirolimus benefits patients with RCC regardless of tumor histology or nephrectomy status. Everolimus, the second mTOR inhibitor to demonstrate activity in RCC, improved progression‐free survival versus placebo in patients whose disease progressed after treatment with vascular endothelial growth factor receptor tyrosine kinase inhibitors (sunitinib, sorafenib, or both); benefit was observed for all risk groups. Deforolimus also exhibited antitumor activity against RCC in early clinical studies. There is now compelling clinical evidence for the effectiveness of targeting mTOR in the treatment of RCC. Cancer 2009. © 2009 American Cancer Society.