alexa PARP Inhibition in Cancer

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PARP Inhibition in Cancer

PARP inhibition can improve survival in cancer patients whose tumors have impaired capacity for homologous recombination, such as germ line or somatic mutations in BRCA. The efficacy of such therapy should be greater if the rate at which cancer cell DNA incurs single-strand breaks is enhanced. Since oxidative stress promotes formation of such breaks, measure which boost oxidative stress in cancer – preferable somewhat selectively – may be worthwhile adjuvants to PARP therapy. In the many cancers that express the Warburg phenomenon, dichloroacetate can promote increased mitochondrial generation of oxidants by directing more pyruvate to oxidation in the Krebs cycle. Concurrent administration of the arthritis drug auranofin could further enhance mitochondrial release of hydrogen peroxide by indirectly inhibiting peroxiredoxin-3, the chief mitochondrial source of peroxidase activity.

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