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Nat Rev Cancer. 2013 Sep;13(9):611-23. doi: 10.1038/nrc3579.

Disrupting proton dynamics and energy metabolism for cancer therapy.

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Institute for Research on Cancer and Aging of Nice (IRCAN), Equipe Labellisée LNCC, University of Nice-Sophia Antipolis, Centre National de la Recherche Scientifique, INSERM, Centre A. Lacassagne, Nice 06189, France.


Intense interest in the 'Warburg effect' has been revived by the discovery that hypoxia-inducible factor 1 (HIF1) reprogrammes pyruvate oxidation to lactic acid conversion; lactic acid is the end product of fermentative glycolysis. The most aggressive and invasive cancers, which are often hypoxic, rely on exacerbated glycolysis to meet the increased demand for ATP and biosynthetic precursors and also rely on robust pH-regulating systems to combat the excessive generation of lactic and carbonic acids. In this Review, we present the key pH-regulating systems and synthesize recent advances in strategies that combine the disruption of pH control with bioenergetic mechanisms. We discuss the possibility of exploiting, in rapidly growing tumours, acute cell death by 'metabolic catastrophe'.

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