Tumor Angiogenesis: A Target for Renal Cell Carcinoma Therapy.Current Perspectives and Novel Strategies

Tumor angiogenesis is a complex multistep process, resulting from the imbalance between pro- and antiangiogenicfactors in tumor environment. A crucial role in this process is played by vascular endothelial growth factor(VEGF). Its expression in metastatic renal cell carcinoma (mRCC) is mostly regulated by hypoxia and it is associated withthe loss of the von Hippel-Lindau (VHL) tumor suppressor gene. The importance of identifying VEGF-independent pathwaysin tumor angiogenesis is increasingly recognized as result of the emerging drug resistance to anti-VEGF therapies.Advances in knowledge of tumor angiogenesis, growth and progression permit to develop new approaches for the treatmentof mRCC, targeting not only VEGF and VEGF tyrosine kinase receptors (VEGFRs) tyrosine kinase pathway, butalso serine/threonine kinases, 51-integrin, AKT, PI3K and STAT3. Starting from sorafenib and sunitinib, several agentshave been approved, with a long list of drugs, as well as axitinib, tivozanib, cediranib and VEGF-Trap, presently in courseof evaluation. Here, we illustrate the principal steps of tumor angiogenic process; showing approved anti-angiogenicagents, the emerging molecules currently under evaluation and some relevant patents.