Hypoxia and metabolism in cancer.

Interest in targeting metabolism has been renewed in recent years as research increases understanding of the altered metabolic profile of tumor cells compared with that of normal cells. Metabolic reprogramming allows cancer cells to survive and proliferate in the hostile tumor microenvironment. These metabolic changes support energy generation, anabolic processes, and the maintenance of redox potential, mechanisms that are all essential for the proliferation and survival of tumor cells. The metabolic switch in a number of key metabolic pathways is mainly regulated by genetic events, rendering cancer cells addicted to certain nutrients, such as glutamine. In addition, hypoxia is induced when highly proliferative tumor cells distance themselves from an oxygen supply. Hypoxia-inducible factor 1α is largely responsible for alterations in metabolism that support the survival of hypoxic tumor cells. Metabolic alterations and dependencies of cancer cells may be exploited to improve anticancer therapy. This chapter reviews the main aspects of altered metabolism in cancer cells, emphasizing recent advances in glucose, glutamine, and lipid metabolism.