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Nat Rev Drug Discov. 2011 Sep 16;10(10):767-77. doi: 10.1038/nrd3554.

Interfering with pH regulation in tumours as a therapeutic strategy.

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Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zürich, Wolfgang Pauli Strasse 10, CH-8093, Zürich, Switzerland.


The high metabolic rate of tumours often leads to acidosis and hypoxia in poorly perfused regions. Tumour cells have thus evolved the ability to function in a more acidic environment than normal cells. Key pH regulators in tumour cells include: isoforms 2, 9 and 12 of carbonic anhydrase, isoforms of anion exchangers, Na+/HCO3- co-transporters, Na+/H+ exchangers, monocarboxylate transporters and the vacuolar ATPase. Both small molecules and antibodies targeting these pH regulators are currently at various stages of clinical development. These antitumour mechanisms are not exploited by the classical cancer drugs and therefore represent a new anticancer drug discovery strategy.

[Indexed for MEDLINE]

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