Updates on novel therapies for metastatic renal cell carcinoma

Abstract

Metastatic renal cell carcinoma (RCC) poses one of the great therapeutic challenges in oncology. RCC is predominantly refractory to treatment with traditional cytotoxic chemotherapies, and until recently management options were limited to immunotherapy or palliative care. However, in the past few years we have experienced a sea change in the treatment of advanced RCC with the introduction of targeted therapies that derive their efficacy at least in part through alterations in tumor angiogenesis. The tyrosine kinase inhibitors sunitinib, pazopanib, and sorafenib, the monoclonal antibody bevacizumab (in combination with interferon-α), and the rapamycin analogs, temsirolimus and everolimus, are now approved agents in the United States for the treatment of metastatic RCC. Efforts to expand upon these successes include developing novel antiangiogenic agents, optimizing concomitant and sequential regimens, identifying predictors of response to specific treatments, and further dissecting the underlying molecular pathogenesis of RCC to reveal novel therapeutic targets.

Keywords: carcinoma; renal cell; therapeutics.

Figure 1.

Therapeutic targets in renal cell carcinoma. AKT, serine/threonine protein kinase; GF, growth factor; GFR, growth factor receptor; HIF, hypoxia-inducible factor; IRS, insulin receptor substrate; mTOR, mammalian target of rapamycin; PDK, pyruvate dehydrogenase kinase; PI3K, phosphatidylinositol 3-kinase; PIP, phosphatidylinositol phosphate; PTEN, phosphatase and tensin homolog; RCC, renal cell carcinoma; RTK, receptor tyrosine kinase; VEGF, vascular endothelial growth factor; VHL, von Hippel–Landau. Modified with kind permission of Springer Science and Business Media from Figure 1 [Courtney and Choueiri, 2009].