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Pan JG, Mak TW: Metabolic targeting as an anticancer strategy: dawn of a new era? . Sci STKE. 2007 Apr 10;2007(381):pe14.
As a result of a spectrum of mitochondrial defects, tumor cells often preferentially use glycolysis to generate adenosine triphosphate (ATP), even in the presence of oxygen, a phenomenon known as aerobic glycolysis, or the "Warburg effect." Dichloroacetate (DCA) is an inhibitor of mitochondrial pyruvate dehydrogenase kinase (PDK), which inhibits pyruvate dehydrogenase (PDH), a gatekeeping enzyme for the entry of pyruvate into the mitochondrial tricarboxylic acid (TCA) cycle. In mice, DCA treatment appears to reactivate mitochondrial respiration in tumor cells, induces their selective killing, and suppresses cancer growth. These observations provide intriguing insights into the plasticity of tumor metabolism that may offer new opportunities for therapeutic intervention. |
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