Tumor angiogenesis and vascular normalization: alternative therapeutic targets Tumor blood vessels are a key target for cancer therapy. Tumor cells secrete high levels of pro-angiogenic factors, leading to the formation of an abnormal vascular network with disorganized, immature, and permeable blood vessels, resulting in poorly perfused tumors. The hypoxic microenvironment created by impaired tumor perfusion can promote the selection of more invasive and aggressive tumor cells and can also impede the tumor-killing action of immune cells. Furthermore, abnormal tumor perfusion reduces the diffusion of chemotherapeutic drugs and radiotherapy efficiency. To combat this defective phenotype, vascular normalization has emerged as a new therapeutic strategy. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. Tumor blood vessels are characterized by their immaturity, which impairs their functionality. The improper development of tumor blood vessels is caused in part by the abnormal levels of growth factors secreted by tumor and stromal cells, among which vascular endothelial growth factor (VEGF) plays a key role. Several other growth factors, including members of the angiopoietins, platelet-derived growth factor (PDGF-B) and transforming growth factor (TGF-β) families, have also been implicated in the formation of a defective vascular network in tumors. Anti-angiogenic therapies could correct the structural and functional flaws of tumor blood vessels, a process referred to as "vascular normalization." The normalization of the tumor vasculature could restore proper blood vessel functions and may help in preventing cancer cells from acquiring an aggressive phenotype associated with a hypoxic microenvironment. Furthermore, increased tumor perfusion would enhance the benefits of chemotherapeutic drugs and radiotherapy. Blood vessels are organized in arteries, veins and capillaries with different morphological structures reflecting their functions in the body. The inner wall of blood vessels is composed of endothelial cells (ECs) forming a monolayer with a streamlined surface, interconnected by junctional molecules such as VE-cadherin and claudins. These ECs are bound to a basal membrane and surrounded by mural cells, which participate in maintaining the cohesion between EC themselves and the basal membrane, and in limiting hyperpermeability and vascular leakage. Angiogenesis refers to the formation of vessels from a preexisting vascular network. Vascular growth during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of ECs, which are regulated by multiple factors among which VEGF plays a critical role.Tumor angiogenesis and vascular normalization: alternative therapeutic targets Tumor blood vessels are a key target for cancer therapy. Tumor cells secrete high levels of pro-angiogenic factors, leading to the formation of an abnormal vascular network with disorganized, immature, and permeable blood vessels, resulting in poorly perfused tumors. The hypoxic microenvironment created by impaired tumor perfusion can promote the selection of more invasive and aggressive tumor cells and can also impede the tumor-killing action of immune cells. Furthermore, abnormal tumor perfusion reduces the diffusion of chemotherapeutic drugs and radiotherapy efficiency. To combat this defective phenotype, vascular normalization has emerged as a new therapeutic strategy. Vascular normalization, by restoring proper tumor perfusion and oxygenation, could limit tumor cell invasiveness and improve the effectiveness of anticancer treatments. Tumor blood vessels are characterized by their immaturity, which impairs their functionality. The improper development of tumor blood vessels is caused in part by the abnormal levels of growth factors secreted by tumor and stromal cells, among which vascular endothelial growth factor (VEGF) plays a key role. Several other growth factors, including members of the angiopoietins, platelet-derived growth factor (PDGF-B) and transforming growth factor (TGF-β) families, have also been implicated in the formation of a defective vascular network in tumors. Anti-angiogenic therapies could correct the structural and functional flaws of tumor blood vessels, a process referred to as "vascular normalization." The normalization of the tumor vasculature could restore proper blood vessel functions and may help in preventing cancer cells from acquiring an aggressive phenotype associated with a hypoxic microenvironment. Furthermore, increased tumor perfusion would enhance the benefits of chemotherapeutic drugs and radiotherapy. Blood vessels are organized in arteries, veins and capillaries with different morphological structures reflecting their functions in the body. The inner wall of blood vessels is composed of endothelial cells (ECs) forming a monolayer with a streamlined surface, interconnected by junctional molecules such as VE-cadherin and claudins. These ECs are bound to a basal membrane and surrounded by mural cells, which participate in maintaining the cohesion between EC themselves and the basal membrane, and in limiting hyperpermeability and vascular leakage. Angiogenesis refers to the formation of vessels from a preexisting vascular network. Vascular growth during development, tissue repair or in disease conditions involves the sprouting, migration and proliferation of ECs, which are regulated by multiple factors among which VEGF plays a critical role.