Clear Renal Cell Carcinoma (cRCC) is a tumour inherently resistant to cytotoxic therapy, radiation, or hormone therapy. Before the advent of Antiangiogenic Agents, the mainstay treatment was based on a cytokine therapy with interferon α (INFα) and interleukin 2 (IL2), despite limited clinical activity and important toxicity. Recent guidelines do not consider the single Agent IFNα as a standard option for Crcc, and recommend the antiangiogenic agents bevacizumab (combined with interferon), sunitinib, and pazopanib as first line therapies in patients with good or intermediate prognosis, based on results from pivotal clinical trials.

The rational to use an antiangiogenic agent in cRCC is based on genetic alterations in the Von Hippel-Lindau gene, reported in 84-98% of sporadic cRCCs. The VHL protein is a component of a ubiquitin ligase complex which recognizes the hypoxia inducible factor (HIF) for proteolysis. Frequent and early loss of heterozygosity in cRCC determines loss of function of VHL protein and HIFα accumulation. HIFα forms a transcriptional complex with HIFβ, which regulates the expression several hypoxia-related genes, including VEGF and PDGF.

This is an interesting case in which molecular knowledge and translation of clinical experience with other cancers result in a good therapeutic opportunity for patients.