The implication of anti-angiogenic treatment of malignancies on human metabolism

As angiogenesis is one of the hallmarks of cancer, a high number of therapeutic strategies have been developed to target the formation of new blood vessels in a growing tumor. Even though clinical efficacy has been documented in some cancer types, it is highly acknowledged that tumors develop resistance to anti-angiogenic therapy. A well-characterized response to anti-angiogenic therapy is the development of intratumoral hypoxia. This, in turn, may lead to specific adaptations in cellular metabolism in order for tumor cells to grow in a nutrient-and oxygen-deprived microenvironment. The presented chapter describes key features of metabolic adaptations in response to induced hypoxia following anti-angiogenic therapy. Importantly, anti-angiogenic therapy can lead to metabolic reprogramming toward anaerobic metabolism where glycolysis is uncoupled from oxidative phosphorylation. This in turn points at potential metabolic targets that may be of importance for the development of combinatorial treatment principles. Moreover, due to intra-and intertumoral heterogeneity, the challenge lies in identifying tumor subtypes that might respond to antimetabolic therapies. Thus, antimetabolic therapies might leverage future anti-angiogenic therapies.