Update on novel agents in renal cell carcinoma.

Renal cell carcinoma (RCC) is a disease with a variable natural history, sometimes presenting with a very indolent course and other times with an aggressive clinical course and unusual sites of metastasis. Surgical resection for stage I-III tumors represents the standard of care and is the only curative option available to patients. However, 40-50% of patients develop metastatic disease. Prior to the advent of targeted therapy, cytokine therapy was the only treatment for RCC. The administration of high-dose, bolus IL-2 has historically produced consistent, durable responses in a small percentage of patients with advanced RCC. The use of IFN-alpha is currently limited to combination therapies. Multiple new agents targeting the VEGF pathway have been tested and approved, including sunitinib, sorafenib and bevacizumab, with others waiting in the wings. In the majority of cases these drugs induce disease stabilization with eventual disease progression. Hence additional new pathways are being targeted and studied. Mechanisms of drug resistance, novel combinations, sequences and schedules are the focus of current clinical investigations. This review provides an updated list of the novel targeted agents in advanced clinical development for metastatic RCC.