mTOR inhibitors in renal cell carcinoma

Progress in the molecular biology of cancer has made possible the discovery of signaling pathways involved in the development and progression of renal cell carcinoma (RCC). One of the most important pathways in the biology of RCC is the PI3K/Akt/mTOR. mTOR is a serine–threonine kinase involved in coupling growth and metabolic signals into stimulation of proliferation and gene expression in cancer and endothelial cells, which ultimately leads to tumor progression. mTOR inhibitors have been tested in several Phase II and III clinical trials in patients with metastatic RCC. Temsirolimus has been demonstrated to significantly improve overall survival and progression-free survival (PFS) of poor-risk metastatic RCC patients compared with interferon (IFN). The efficacy of temsirolimus has been observed both in nephrectomized and non-nephrectomized patients irrespective of the histological type of RCC. Everolimus administered to metastatic RCC patients following failure of one or two anti-VEGFR tyrosine kinase inhibitor-based regimens has made a significant prolongation of PFS compared with placebo possible.