Tumor angiogenesis and vascular normalization: alternative therapeutic targets

Abstract Tumor blood vessels are a key target for cancertherapeutic management. Tumor cells secrete high levels ofpro-angiogenic factors which contribute to the creation ofan abnormal vascular network characterized by disorga nized, immature and permeable blood vessels, resulting inpoorly perfused tumors. The hypoxic microenvironmentcreated by impaired tumor perfusion can promote theselection of more invasive and aggressive tumor cells andcan also impede the tumor-killing action of immune cells.Furthermore, abnormal tumor perfusion also reduces thediffusion of chemotherapeutic drugs and radiotherapyefficiency. To fight against this defective phenotype, thenormalization of the tumor vasculature has emerged as anew therapeutic strategy. Vascular normalization, byrestoring proper tumor perfusion and oxygenation, couldlimit tumor cell invasiveness and improve the effectivenessof anticancer treatments. In this review, we investigate themechanisms involved in tumor angiogenesis and describestrategies used to achieve vascular normalization.