Role of Lactate Dehydrogenase in Tumor Metabolism and Progress of LDH-targeted Drugs

Abstract

Abnormal energy metabolism is one of the main hallmarks of cancer. Studies have shown that tumor cells, even in the presence of oxygen, favored glycolysis to produce lactic acid and a small amount of ATP with the help of LDHA in the cytosol (the famous Warburg effect). The excessive lactate is then exported to the extracellular space in the presence of monocarboxylate transporters (MCTs, primarily MCT4), resulting in the decrease of microenvironment pH value. On the other hand, the lactate in the tumor microenvironment will be re-absorbed in adjacent oxygenated tumor cells through the transporter MCT1 and finally transformed into pyruvate for oxidative phosphorylation under the effect of LDHB. The important effects of LDH in tumor energy metabolism reprogramming make it a new target for tumor therapy. In this review, we discussed briefly on the relation between LDH and energy metabolism of tumor cells, especially its effects on the process of tumor as well as the progress of LDH-targeted anti-tumor drugs.

Keywords

• lactate
• lactic dehydrogenase
• warburg effect
• pyruvate metabolism