Targeting angiogenesis in renal cell carcinoma

Introduction: Understanding the molecular pathogenesis of renal cell carcinomas (RCC) has identified targets for therapeutic intervention. The recognition of the importance of hypoxia-inducible factor-1 alpha (HIF-1 alpha) signaling in the pathogenesis of clear-cell RCC has led to widespread study of angiogenesis inhibitors. While the major component of the angiogenic process in RCC is VEGF, targeting of the mTOR pathway is important because activation of the upstream PI3K/Akt/mTOR signaling pathways is one method by which constitutive HIF-1 alpha activation or upregulation occurs. Areas covered: Current FDA-approved anti-angiogenic agents as first-and second-line treatment for RCC, as well as agents in development will be reviewed. Expert opinion: Novel agents targeting non-VEGFR signals in kidney cancer will be met with new successes and new challenges in therapeutic development. While several of these agents will likely show activity, they may accentuate toxicity. Careful triage of these agents paired with biomarker studies will facilitate development of these agents and identification of those patients most likely to benefit from these emerging therapies.