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Several alternative treatments have recently been developed for metastatic renal cell carcinoma (RCC). Vascular endothelial growth factor (VEGF) is a potent pro-angiogenic protein, which is responsible for increased vasculature and tumor-growth in RCC. Fundamentally, a mutation in the von Hippel-Lindau (VHL) tumor suppressor gene induces overexpression of VEGF via accumulation of hypoxia-inducible factor (HIF)-1 in RCC. Several agents inhibiting the VEGF signaling cascade, such as sorafenib, sunitinib and bevacizumab, have been found to exert significant anti-tumor effects and provide meaningful clinical benefits. Furthermore, temsirolimus and everolimus, inhibitors of the mammalian target of rapamycin (mTOR), which block the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway involved in numerous cellular functions including cell proliferation, survival and angiogenesis, have been found to be effective agents against advanced RCC in the clinical setting. Although molecular targeting therapies against the VEGF or mTOR signaling pathway have revolutionized the treatment of advanced RCC, no curative therapy has yet been established.

Anticancer Target Molecules Against the SCF Ubiquitin E3 Ligase in RCC: Potential Approaches to the NEDD8 Pathway