The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia

• DOI: 10.1038/ncomms12308
• Publication Date: 2016-07-25T09:33:08Z
• Authors: Thomas M. Ashton; Emmanouil Fokas; Leoni A. Kunz-Sch...; Lisa K. Folkes; Selvakumar Anbalagan; Melanie Huether; Catherine J. Kelly; Giacomo Pirovano; Francesca M. Buffa; Ester M. Hammond; Michael Stratford; Ruth J. Muschel; Geoff S. Higgins; William Gillies M...
• Keywords: Atovaquone; Hypoxia; Radiosensitivity

Abstract Tumour hypoxia renders cancer cells resistant to therapy, resulting in markedly worse clinical outcomes. To find candidate compounds that reduce tumours, we conduct a high-throughput screen for oxygen consumption rate (OCR) reduction and identify number of drugs with this property. For study focus on the anti-malarial, atovaquone. Atovaquone rapidly decreases OCR by more than 80% wide range cell lines at pharmacological concentrations. In addition, atovaquone eradicates FaDu, HCT116 H1299 spheroids. Similarly, it reduces FaDu xenografts nude mice, causes significant tumour growth delay when combined radiation. is ubiquinone analogue, inhibiting mitochondrial complex III. We are now undertaking studies assess whether patients, thereby increasing efficacy radiotherapy.