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. Author manuscript; available in PMC: 2018 Jan 19.
Published in final edited form as: Nat Rev Nephrol. 2017 Jan 19;13(2):69–70. doi: 10.1038/nrneph.2016.194

Figure 1. Current and future anti-angiogenic therapies.

Figure 1

Loss of VHL is a common genetic feature in clear cell renal cell carcinoma that leads to the accumulation of hypoxia inducible factor (HIF)-1α and HIF-2α, and expression of pro-angiogenic factors such as vascular endothelial growth factor (VEGF), G1/S specific cyclin D1 and glucose transporter type 1 (GLUT 1). Current anti-angiogenic tyrosine kinase inhibitors (sunitinib, pazopanib, sorafenib, axitinib, bevacizumab) treat kidney cancer by targeting VEGF-dependent pathways at the tumour–endothelium interface. New agents including lenvatinib and cabozantinib also target other tyrosine kinases (VEGFR receptor (VEGFR), hepatocyte growth factor receptor (c-MET), fibroblast growth factor receptor (FGFR)) thought to be critical for resistance to VEGF-directed therapy. A novel class of agents that inhibit HIF-2α-dependent transcription (PT2399 and PT2385) has been developed. These molecules target more directly key pathways in kidney tumorigenesis, downstream of VHL loss. HGF, hepatocyte growth factor; FGF, fibroblast growth factor.