The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia
Citations Over TimeTop 10% of 2016 papers
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.
Related Papers
- → Atovaquone in the Treatment of Babesia microti Infections in Hamsters(1996)88 cited
- → Successful Prevention and Treatment of Babesiosis with Atovaquone(1995)66 cited
- Persistence of atovaquone in human sera following treatment: inhibition of Plasmodium falciparum development in vivo and in vitro.(2003)
- → Therapeutic Efficacy of Atovaquone against the Bovine Intraerythrocytic Parasite, Babesia divergens(1997)53 cited
- → PERSISTENCE OF ATOVAQUONE IN HUMAN SERA FOLLOWING TREATMENT: INHIBITION OF P. FALCIPARUM DEVELOPMENT IN VIVO AND IN VITRO(2003)28 cited