Angiognesiss Revisited: Role and (Therapeutic) Implications of Endothelial Metabolism

Angiogenesis, the growth of new blood vessels, plays a crucial role in numerous diseases, including cancer. Anti-angiogenesis therapies have been developed to starve cancer cells from nutrients. Clinically approved anti-angiogenic drugs prolong the survival of cancer patients, but their success is limited by intrinsic refractoriness and acquired resistance. New strategies are thus needed to block tumor angiogenesis via alternative mechanisms. We recently reported that PFKFB3-driven glycolysis regulates the endothelial tip cell function during vessel sprouting, even capable of overruling the potent pro-stalk activity of Notch, and that its loss in endothelial cells causes vascular hypobranching defects. Moreover, partial and transient reduction of glycolysis by blocking PFKFB3 reduced pathological angiogenesis in several disease models. Ongoing studies explore the role of lipid and amino acid metabolism in vessel sprouting, and assess the therapeutic potential of targeting these metabolic pathways for anti-angiogenic therapy.