mTOR inhibitors: temsirolimus and everolimus in the treatment of renal cell carcinoma

mTOR signaling pathway (mammalian target of rapamycin) is a major pathway in cell physiology and malignant behavior implicated in cell growth, cell proliferation, cell metabolism, protein synthesis and angiogenesis. Temsirolimus has shown in a randomized phase III trial for patients with poor risk feature of metastatic renal cell carcinoma, a significant gain in overall survival compared to this obtained with alpha interferon (7.3 a 10.9 months; HR: 0.73; P < 0.0069). Everolimus has shown in a randomized phase III trial for patients with metastatic renal cell carcinoma having failed under VEGFR tyrosine kinase inhibitor a significant gain in progression-free survival compared to this obtained with placebo VEGFR (1,8 a 4,6 months; HR: 0.33; P < 0.001). Temsirolimus and everolimus are now part of the reference treatments in renal cell carcinoma. This paper is a review of these two drugs in this setting.