Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 10, Issue 10, Pages 767-777Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nrd3554
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Funding
- European Union
- ETH Zurich
- Swiss National Science Foundation
- SwissBridge Foundation
- Stammbach Foundation
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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.
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