Intervention on lactate in cancer: A promising approach for the development of cancer therapeutics

Lactate, the main product of tumor glycolysis is considered one of the most crucial metabolites in the tumor microenvironment. The reprogrammed cancer cell metabolism is closely associated with the enhanced rate of tumor glycolysis leading to excess lactate production concomitant with increased extracellular acidification. This decline in pH in the vicinity of cancer cells is largely attributed to reprogrammed tumor glycolysis (Warburg effect). Substantial literature data to date suggest that lactate is not merely a waste product of tumor glycolysis, albeit serves as the main fuel to meet the anabolic requirements of cancer cells. Lactate plays a critical role in tumor growth, migration and invasion, tumor metastasis, tumor microenvironment and immune modulation. This review summarizes the current knowledge about the role of lactate in tumor glycolysis, its fate and transporters, lactate shuttle, and metabolic symbiosis. It also condenses the role of lactate in the tumor microenvironment and immune invasion and the development of therapeutic strategies.