Abstract
After the first report demonstrating efficacy of an anti-angiogenic treatment in patients suffering from metastatic renal cell cancer in 2003, intense developments of VEGF monoclonal antibodies or tyrosine kinases inhibitors directed against VEGF receptors were done. This approach was successful and lead to the registration of anti angiogenic agents in at least 8 types of different cancers. Metastatic renal carcinoma, a chemo resistant tumor, appears to be very sensitive to these agents. Today several different agents, directly or undirectly aimed at the VEGF pathway, are available for treatment. Indeed, the clear cell renal carcinoma that represents more than 75% of cases, commonly achieved some inactivation of the Von Hippel Lindau (VHL) gene. As a consequence, the hypoxia inductive factor (HIF) accumulates in tumor cells, leading to the upregulation downstream genes, particularly VEGF and PDGF. In addition, renal cell carcinoma cells produce high amounts of VEGF and overexpressed different types of VEGF receptors. The specific carcinogenesis explains that anti-angiogenic agents have double targets in this tumor: the endothelial cells of the neo-vascularization as well as tumor cells.
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