Target therapy in metastatic renal cell carcinoma

Metastatic RCC with 38,000 new cases diagnosed in the United States every year is notoriously resistant to conventional chemotherapy and is almost invariably an incurable condition. New biologic drugs are beginning to break this resistance, reflecting in the registration of four innovative agents for treatment of advanced RCC in the last 2 years, bevacizumab, sorafenib, sunitinib and temsirolimus. Small-molecule multikinase inhibitors targeting VEGF receptors (sunitinib and sorafenib) can prolong time to progression and preserve quality of life when used in newly diagnosed or previously treated patients. The anti-VEGF antibody bevacizumab enhances response rate and prolongs disease control when added to interferon. Temsirolimus, mammalian target of rapamycin inhibitor, prolongs the survival duration of patients with poor-risk disease. In this review, we report pre-clinical data, data relative to registrative phase III trials, and guideline indications for an optimal use of these new agents that are revolutionising the management of metastatic Renal Cell Carcinoma.