Metabolic effects of antiangiogenic drugs in tumors: therapeutic implications.

Antiangiogenic therapy has become a mainstay of cancer therapeutics, but clinical responses are generally short-term owing to the development of secondary resistance. Tumor starvation by antiangiogenic drugs is largely attributed to increased hypoxia and impaired nutrients supply, suggesting that angiogenesis inhibition causes remarkable metabolic perturbations in the tumor microenvironment. We review here recent acquisitions concerning metabolic effects of angiogenesis blockade in tumors and discuss the possibility that some metabolic features of tumor cells - i.e. their dependency from glucose as primary energy substrate - might affect tumor responses to anti-vascular endothelial growth factor treatment. Moreover, we discuss the hypothesis that anti-angiogenic therapy might foster metabolic evolution of tumors. The therapeutic implications of this hypothesis will be discussed further here.