Journal article
The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia
- Abstract:
- Tumour hypoxia renders cancer cells resistant to cancer therapy, resulting in markedly worse clinical outcomes. To find clinical candidate compounds that reduce hypoxia in tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify a number of drugs with this property. For this study we focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases the OCR by more than 80% in a wide range of cancer cell lines at pharmacological concentrations. In addition, atovaquone eradicates hypoxia in FaDu, HCT116 and H1299 spheroids. Similarly, it reduces hypoxia in FaDu and HCT116 xenografts in nude mice, and causes a significant tumour growth delay when combined with radiation. Atovaquone is a ubiquinone analogue, and decreases the OCR by inhibiting mitochondrial complex III. We are now undertaking clinical studies to assess whether atovaquone reduces tumour hypoxia in patients, thereby increasing the efficacy of radiotherapy.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.3MB, Terms of use)
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- Publisher copy:
- 10.1038/ncomms12308
Authors
- Publisher:
- Nature Publishing Group: Nature Communications
- Journal:
- Nature communications More from this journal
- Volume:
- 7
- Pages:
- 12308
- Publication date:
- 2016-07-25
- Acceptance date:
- 2016-06-17
- DOI:
- ISSN:
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2041-1723
- Pmid:
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27453292
- Language:
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English
- Subjects:
- Pubs id:
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pubs:636321
- UUID:
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uuid:15d89091-2bfd-4609-80fa-c5157ea5d1c9
- Local pid:
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pubs:636321
- Source identifiers:
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636321
- Deposit date:
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2017-10-19
Terms of use
- Copyright holder:
- Ashton et al
- Copyright date:
- 2016
- Notes:
- Copyright The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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