Question ID: WS-126
Submitted by: Marc Wathelet
April 2, 2012
Targeting the Warburg effect: sponsoring clinical trials for dichloroacetate with public funds BACKGROUND: cancer cells often display abnormal metabolism and mitochondrial function, which involve a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis (Warburg effect). Dichloroacetate (DCA) has been shown to reverse this metabolic shift by targeting the enzyme pyruvate dehydrogenase kinase, resulting in normalization of the hyperpolarized state of mitochondria, increased reactive oxygen species production and induction of apoptosis in cancer cells (the work of E.D. Michelakis in Canada). DCA is a small, simple, very cheap molecule, it has been used in humans for rare indications for many years, but it cannot be patented, precluding any interest by pharmaceutical companies, the main sponsors of clinical trials. FEASIBILITY: peripheral neuropathy is the known side effect of DCA but the effect is reversible. A first publication indicated clinical efficacy was present at a dose that did not cause neuropathy. Appropriation of money to test in clinical trials such a promising drug by either the NCI or congress is practical but a political decision and lobbyists from pharmaceutical companies are likely opposed. IMPLICATIONS FOR PUBLIC HEALTH: should DCA prove effective for a substantial proportion of cancers, the public health implications would be huge in terms of live saved and health care cost reduction.
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