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Metabolites 2018, 8(1), 13; https://doi.org/10.3390/metabo8010013

Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness

1
Cancer Research UK Edinburgh Centre and Division of Pathology Laboratory, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK
2
Royal (Dick) School of Veterinary Studies and Roslin Institute, The University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
3
Institute of Sensors, Signals and Systems, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh EH14 4AS, UK
*
Author to whom correspondence should be addressed.
Received: 12 January 2018 / Revised: 6 February 2018 / Accepted: 7 February 2018 / Published: 10 February 2018
(This article belongs to the Special Issue Carbonic Anhydrases and Metabolism)
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Abstract

Carbonic anhydrase IX has been under intensive investigation as a therapeutic target in cancer. Studies demonstrate that this enzyme has a key role in pH regulation in cancer cells, allowing these cells to adapt to the adverse conditions of the tumour microenviroment. Novel CAIX inhibitors have shown efficacy in both in vitro and in vivo pre-clinical cancer models, adversely affecting cell viability, tumour formation, migration, invasion, and metastatic growth when used alone. In co-treatments, CAIX inhibitors may enhance the effects of anti-angiogenic drugs or chemotherapy agents. Research suggests that these inhibitors may also increase the response of tumours to radiotherapy. Although many of the anti-tumour effects of CAIX inhibition may be dependent on its role in pH regulation, recent work has shown that CAIX interacts with several of the signalling pathways involved in the cellular response to radiation, suggesting that pH-independent mechanisms may also be an important basis of its role in tumour progression. Here, we discuss these pH-independent interactions in the context of the ability of CAIX to modulate the responsiveness of cancer to radiation. View Full-Text
Keywords: carbonic anhydrase IX; cancer; hypoxia; radiation; resistance carbonic anhydrase IX; cancer; hypoxia; radiation; resistance
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Ward, C.; Meehan, J.; Gray, M.; Kunkler, I.H.; Langdon, S.P.; Argyle, D.J. Carbonic Anhydrase IX (CAIX), Cancer, and Radiation Responsiveness. Metabolites 2018, 8, 13.

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