Recent advances in the treatment of metastatic renal cell carcinoma.

In the past 5 years, the treatment of patients with metastatic renal cell carcinoma has changed dramatically from being largely cytokine-based with the emergence of targeted therapy. Following the elucidation of various molecular pathways in renal cell carcinoma, targeted agents (particularly vascular endothelial growth factor-targeting antiangiogenic agents) now form the backbone of most therapeutic strategies for patients with metastatic renal cell carcinoma and the outcome of treatment has improved. However, many tumors eventually develop resistance to targeted therapy due to secondary mutation of the target protein or compensatory changes within the target pathway that bypass the site of inhibition. On the other hand, there are new forms of immunotherapy that hold the promise of improving the outcome for patients with metastatic renal cell carcinoma. In this article, we describe some of these new therapies, including the anti-vascular endothelial growth factor monoclonal antibody bevacizumab, several receptor tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, axitinib, and tivozanib), the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and new immunotherapy modalities, such as anti-cytotoxic T-lymphocyte-associated antigen 4 antibody and anti-programmed cell death 1/programmed cell death-ligand 1 antibody. We also discuss their role in the current management of patients with metastatic renal cell carcinoma.