Effective therapies to fight cancer should not be focused specifically on cancer cells, but it should consider the various components of the TME. Non-cancerous cells cooperate with cancer cells by sharing signaling and organic molecules, accounting for cancer progression. Most of the anti-angiogenic therapy clinically approved for the treatment of human diseases relies on targeting vascular endothelial growth factor (VEGF) signaling pathway. Unexpectedly and unfortunately, the results of anti-angiogenic therapies in the treatment of human diseases are not so effective, showing an insufficient efficacy and resistance.This chapter will give some insights on showing that targeting endothelial cell metabolism is a missing piece to revolutionize cancer therapy. Only recently endothelial cell (EC) metabolism has been granted as an important inducer of angiogenesis. Metabolic studies in EC demonstrated that targeting EC metabolism can be an alternative to overcome the failure of anti-angiogenic therapies. Hence, it is urgent to increase the knowledge on how ECs alter their metabolism during human diseases, in order to open new therapeutic perspectives in the treatment of pathophysiological angiogenesis, as in cancer.
Keywords: Angiogenesis; Cancer progression; Cancer therapy; Endothelial differentiation; Metabolic remodeling; Tumor microenvironment (TME).