The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia
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 thi...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Publishing Group: Nature Communications
2016
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| Subjects: |
| _version_ | 1826260592808165376 |
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| author | Ashton, T Fokas, E Kunz-Schughart, L Folkes, L Anbalagan, S Huether, M Kelly, C Pirovano, G Buffa, F Hammond, E Stratford, M Muschel, R Higgins, G McKenna, W |
| author_facet | Ashton, T Fokas, E Kunz-Schughart, L Folkes, L Anbalagan, S Huether, M Kelly, C Pirovano, G Buffa, F Hammond, E Stratford, M Muschel, R Higgins, G McKenna, W |
| author_sort | Ashton, T |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-06T19:08:07Z |
| format | Journal article |
| id | oxford-uuid:15d89091-2bfd-4609-80fa-c5157ea5d1c9 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:08:07Z |
| publishDate | 2016 |
| publisher | Nature Publishing Group: Nature Communications |
| record_format | dspace |
| spelling | oxford-uuid:15d89091-2bfd-4609-80fa-c5157ea5d1c92022-03-26T10:27:52ZThe anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxiaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:15d89091-2bfd-4609-80fa-c5157ea5d1c9Cancer metabolismCancer therapyEnglishSymplectic Elements at OxfordNature Publishing Group: Nature Communications2016Ashton, TFokas, EKunz-Schughart, LFolkes, LAnbalagan, SHuether, MKelly, CPirovano, GBuffa, FHammond, EStratford, MMuschel, RHiggins, GMcKenna, WTumour 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. |
| spellingShingle | Cancer metabolism Cancer therapy Ashton, T Fokas, E Kunz-Schughart, L Folkes, L Anbalagan, S Huether, M Kelly, C Pirovano, G Buffa, F Hammond, E Stratford, M Muschel, R Higgins, G McKenna, W The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title | The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title_full | The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title_fullStr | The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title_full_unstemmed | The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title_short | The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| title_sort | anti malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia |
| topic | Cancer metabolism Cancer therapy |
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