Journal article
Increasing radiosensitivity by alleviating tumour hypoxia: a drug screen reveals atovaquone as a clinical candidate
- 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 conducted a high throughput screen for oxygen consumption rate (OCR) reduction and identified a number of drugs with this property. For this study we focused on the antimalarial, 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 virtually eliminates 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
- Journal:
- Nature Communications More from this journal
- Volume:
- 7
- Article number:
- 12308
- Publication date:
- 2016-06-01
- Acceptance date:
- 2016-06-17
- DOI:
- ISSN:
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2041-1723
- Pubs id:
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pubs:633477
- UUID:
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uuid:c0976293-ae5d-4422-95a2-d5cf0077bcd9
- Local pid:
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pubs:633477
- Source identifiers:
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633477
- Deposit date:
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2016-07-12
- ARK identifier:
Terms of use
- Copyright holder:
- Ashton et al
- Copyright date:
- 2016
- Notes:
- 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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