Inhibition of glycolysis as a therapeutic strategy in acute myeloid leukemias

Abstract

The metabolic pathways in cancer cells are reprogrammed such that they utilize nutrients quite differently than their normal, nonmalignant counterparts. It has been known for some time that the cancer phenotype results in alterations to glucose metabolism and, more recently, modifications to both glutamine and fatty acid metabolism have been noted. So prevalent is this altered metabolism in malignancy that many now consider it a hallmark of the cancer phenotype. As such, the metabolic discrepancies between cancer cells and normal cells provide a therapeutic window for the potential development of targeted anticancer agents. A number of pharmacological agents that either directly target the enzymes driving tumor glycolysis or the upstream mediators of the glycolytic pathway are currently under investigation with the hope of combining them with existing clinical protocols. Akin to the cytokines and chemokines produced by cancer cells, the intermediates and byproducts of altered tumor glycolysis, upon secretion from cancer cells, are also capable of modulating the phenotypes of normal cells located in the tumor microenvironment. Thus, glycolytic inhibitors may also rescue the effects that tumor derived metabolites have on surrounding cells.