ical trial has shown that BVZ can significantly prolong the time to progression of disease in patients with metastatic renal-cell cancer. However, only the BVZ plus interferon alpha treatment has obtained approval by the Food and Drugs SKI-II biological activity administration in the United States of America and the European Medicines Agency in Europe following phase III clinical assays. These clinical assays have demonstrated an increase in progression-free survival associated with the treatment combining IFN and BVZ 
compared to IFN alone. Unfortunately, BVZ plus IFN did not improve overall survival when compared to IFN monotherapy. Other treatments targeting the different VEGF receptors are Receptor Tyrosine Kinase Inhibitors such as sunitinib targeting VEGFR2, PDGFR, FLT3, and c-Kit or sorafenib targeting B-Raf, c-Raf, VEGFR2/3, PDGFR, FLT3, and c-Kit. These compounds are used in cases of advanced RCC with good or intermediate prognosis. Two clinical trials showed the benefit of using sunitinib for treating advanced RCC with a greater decrease in tumour size, an increase of progression-free survival of about nine months, and a better quality of life. Another phase III clinical trial has also PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19835934 demonstrated efficacy of sorafenib on RCC. However, as for the BVZ plus IFN combined treatment, sunitinib or sorafenib did not increase overall survival of RCC patients. Axitinib and pazopanib are new VEGFR-TKI compounds generated for the treatment of RCC but it is too early to evaluate their efficacy compared to 2 sorafenib or sunitinib. The other class of compounds targets the mTOR pathway. Patients who progressed on sorafenib or sunitinib as well as patients who have a poor prognosis are treated with mTOR blockers such as temsirolimus or everolimus. Deforolimus is also a new generation of anti-mTOR compounds for the treatment of RCC. Journal of Nucleic Acids noted as VEGFxxx. The major ones are VEGF165, VEGF189, and VEGF121. There are also a few minor isoforms spliced from the pre-mRNA, which are VEGF206, VEGF183, VEGF145 and VEGF148, and VEGF111 although their functions remain less clear . In 2002 Bates et al. identified a splice variant of VEGF165, VEGF165b that is expressed in most normal tissues and downregulated in cancers especially in RCC. Furthermore, this finding could put a full stop to the paradox of a high level of VEGF in podocytes where angiogenesis is not upregulated. As suggested by Bates and Harper, the codiscoverers of VEGFxxxb, the existence of anti-angiogenic forms of VEGF “needs reinterpretation or at worst, require repeating the experiment with reagent that differentiate between isoforms families”. In light of the discovery of Bates et al., these forms of VEGF may be anti-angiogenic forms. After the identification of VEGF165b, a new sub-family of VEGFxxxb isoforms were identified . Since then, a few publications assessed the antiangiogenic or at least a less angiogenic outcome of VEGFxxxb isoforms by, in particular, the downregulation of VEGFR signalling pathway and a decrease of tumour growth. These results have been achieved in vitro on proliferation and migration of endothelial cells along with in vivo studies on tumour volume of RCC, prostate, melanoma, and colorectal cancers and on experimental choroidal neovascularization. Moreover, the downregulation of VEGF165b expression leads to metastatic melanoma while VEGF165b expression prevents metastasis of malignant melanoma. We can hypothesize that the ratio between the pro- and the anti-angiogeni