Cancer metabolism as a therapeutic target: metabolic synthetic lethality.

Interest in targeting metabolism as a possible cancer therapy has been renewed in recent years as research increases our understanding of the altered metabolic profile of cancer cells compared with that of normal cells. As mentioned by Drs. Batra, Rosen, and Shanmugam, metabolic reprogramming allows tumor cells to survive and proliferate in the hostile tumor environment. Alterations in tumor cell metabolism lead to higher energy production, induction of anabolic pathways, and maintenance of cellular redox potential. These mechanisms are essential for the survival and proliferation of tumor cells. Metabolic processes are regulated by genetic events that render cancer cells dependent on certain nutrients, such as glutamine and lipids. Moreover, hypoxia in cancer cells that are distant from their oxygen supply will lead to the induction of hypoxia-inducible factor 1α (HIF-1α), a transcription factor that is responsible for changes in metabolism that support the survival of cells in hypoxic tumor areas. Several aspects of metabolism are altered in tumor cells—including glucose and glutamine metabolism, as the authors have mentioned—but we would like to point out that lipid metabolism also has a crucial role in tumorigenesis.