EPAS1 and renal cell carcinoma: Several studies of renal cell carcinoma and hepatocellular carcinoma treated with VEGF tyrosine kinase inhibitors sunitinib [53] and sorafenib [54] found that downregulation of HIF-1α and upregulation of HIF-2α with treatment can further stimulate the production of pro-angiogenic factors and cytokines to foster vascular endothelial cell proliferation.