Regulation Of Cancer Cell Metabolism By Hypoxia

The growth of a tumor usually results in the development of hypoxia, which is primarily a consequence of the tumor outgrowing existing vasculature and the disorganized nature of vascular growth induced by the tumor itself. The low oxygen tension at the site of neoplastic growth has a significant effect on the metabolic status of the cells involved. In order for the cells to survive the harsh conditions of low oxygen and nutrition, the metabolism of the cell switches from an aerobic type of metabolism to an anaerobic one, relying primarily on glycolysis for the production of energy and metabolic intermediates that feed various biosynthetic pathways. Because this phenotype is associated with increased cell survival, drug resistance, and ultimately poor patient prognosis, the metabolic components and the mediators of the hypoxic response are viable targets in the war on cancer. Currently, a variety of drugs are being explored that influence the mediators of the hypoxic response, such as hypoxia-inducible factor-1 (HIF-1), and those that target metabolic enzymes directly. These agents show promise in improving the current standard of care by acting in a synergistic manner with current cancer therapies.