Targeting cancer metabolism
The Warburg effect occurs in 90% of tumors, where glycolysis is favored despite the presence of oxygen. The activity of pyruvate dehydrogenase kinases (PDKs) is increased in cancer cells, suppressing glucose oxidation. Inhibition of PDKs can redirect glucose flux into the mitochondria, reversing the Warburg effect. Dichloroacetate (DCA) is a relatively non-toxic PDK inhibitor that inhibits all four isoforms of PDK with differing potency. We examined the determinants of DCA sensitivity, the...[Show more]
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