Lactate and malignant tumors: a therapeutic target at the end stage of glycolysis

• Published in: Journal of bioenergetics and biomembranes 2007-02, Vol.39 (1), p.73-77
• Main Authors: Mathupala, Saroj P, Colen, Chaim B, Parajuli, Prahlad, Sloan, Andrew E
• Format: Article
• Language: English
• Subjects: Adaptation; Animals; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Brain tumors; Cancer; Drug development; Efflux; Glioma; Glycolysis; Glycolysis - drug effects; Glycolysis - physiology; Humans; L-Lactate Dehydrogenase - antagonists & inhibitors; L-Lactate Dehydrogenase - metabolism; Lactic acid; Lactic Acid - biosynthesis; Metabolic flux; Metabolic Networks and Pathways - drug effects; Metabolic pathways; Microenvironments; Monocarboxylic Acid Transporters - metabolism; Pathways; Power plants; Pyruvic acid; Pyruvic Acid - metabolism; Therapeutic targets; Tumors
• ISSN: 0145-479X; 1573-6881
• DOI: 10.1007/s10863-006-9062-x

Metabolic aberrations in the form of altered flux through key metabolic pathways are primary hallmarks of many malignant tumors. Primarily the result of altered isozyme expression, these adaptations enhance the survival and proliferation of the tumor at the expense of surrounding normal tissue. Consequently, they also expose a unique set of targets for tumor destruction while sparing healthy tissues. Despite this fact, development of drugs to directly target such altered metabolic pathways of malignant tumors has been under-investigated until recently. One such target is the ultimate step of glycolysis, which, as expected, presents itself as a metabolic aberration in most malignant tumors. Termed "aerobic glycolysis" due to abnormal conversion of pyruvic acid to lactic acid even under normoxia, the altered metabolism requires these tumors to rapidly efflux lactic acid to the microenvironment in order to prevent poisoning themselves. Thus, exposed is a prime "choke-point" to target these highly malignant, frequently chemo- and radio- resistant tumors. This review will focus on current outcomes in targeting lactate efflux in such tumors using glioma as a model, an ongoing project in our laboratory for the past half-decade, as well as supporting evidence from recent studies by others on targeting this "tail-end" of glycolysis in other tumor models.