[Renal cell carcinoma]

Abstract

Clear cell renal cell carcinoma(ccRCC)with a von Hippel-Lindau(VHL)gene alteration is the most frequent histological phenotype of renal cell cancer(RCC). This gene alteration suppresses ubiquitination and increases hypoxia-inducible factor (HIF)-alpha accumulation, resulting in the upregulation of HIF-alpha target genes, which in turn leads to hypervascular tumor formation. Sorafenib, sunitinib, axitinib, and pazopanib are kinase inhibitors that block vascular endothelial growth factor receptor(VEGFR). Other families of targeted drugs for RCC are antibodies against VEGF, such as bevacizumab, and mammalian target of rapamycin inhibitors, such as temsirolimus and everolimus, which exert anti-angiogenic effects by downregulating HIF-alpha expression. Thus, the newly developed targeted drugs for RCC are classified as anti-angiogenic drugs. However, the frequency of a sustained complete response(CR)in response to these drugs is quite low, indicating that the exploration of other modalities of treatment, besides anti-angiogenic drugs, is warranted.