Lactate and malignant tumors: A therapeutic target at the end stage of glycolysis
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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.
KeywordsLactate MCT Monocarboxylate transport Glioma Malignant tumors
small intefering RNA
cluster of differentiation
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- Berg JM, Tymoczko JL, Stryer L (2006) Biochemistry. 6th ed. New York, WH FreemanGoogle Scholar
- Colen CB, Seraji-Bozorgzad N, Marples B, Galloway MP, Sloan AE, Mathupala SP (2006) Neurosurgery 59:1313–1324Google Scholar
- Fang J, Quinones QJ, Holman TL, Morowitz MJ, Wang Q, Zhao H, Sivo F, Maris JM, Wahl ML (2006) Mol Pharmacol 70:2108–2115Google Scholar
- Warburg O, Dickens F, Kaiser Wilhelm-Institut für Biologie B (1930) The metabolism of tumours: investigations from the Kaiser-Wilhelm Institute for Biology. Berlin-Dahlem, London, ConstableGoogle Scholar