**4. Targeting HIF-responsive growth factors**

## **4.1. Vascular endothelial growth factor**

Clear cell renal carcinomas are notoriously angiogenic. Indeed, prior to the availability of computed tomography, renal angiograms were often used to diagnose these tumors. Renal carcinomas overproduce a variety of angiogenic moieties including vascular endothelial growth factor (VEGF), the product of a HIF-responsive gene. In addition to promoting angiogenesis, VEGF might suppress antitumor immune responses as well. It has also been suggested that VEGF has direct stimulatory effects on renal carcinoma cells, although these findings await further corroboration, [8, 9].

Several drugs that inhibit VEGF, or its kinase insert domain-containing receptor (KDR), have activity against clear cell renal carcinomas. In a randomized phase II study, patients with metastatic renal carcinoma who were treated with 10 mg/kg (but not 3 mg/kg) bevacizumab, a neutralizing antibody against VEGF, exhibited a significant delay in time-to-disease pro‐ gression, [10]. Other unrelated KDR inhibitors such as SU11248 (sunitinib maleate), BAY43-9006 (sorafenib), and AG-013736 also appear to have significant activity against this tumor subtype, [11, 12].
