An anti-malaria drug could help radiotherapy destroy tumours according to a Cancer Research UK-funded study published in Nature Communications today.
The study, carried out at the Cancer Research UK Radiation Research Centre in Oxford, looked at the effect of the drug, called atovaquone*, on tumours with low oxygen levels in mice to see if it could be repurposed to treat cancer.
Radiotherapy works by damaging the DNA in cells. A good supply of oxygen reduces the ability of cancer cells to repair broken DNA. So when a tumour has low levels of oxygen, it can repair itself more easily after radiotherapy.
This means that tumours with low oxygen levels are more difficult to treat successfully with radiotherapy. They are also more likely to spread to other parts of the body.
This research showed for the first time that an anti-malaria drug slows down the rate at which cancer cells use oxygen by targeting the mitochondria, the powerhouses of the cell that make energy, a process that uses oxygen.
By slowing down the use of oxygen, this drug reverses the low-oxygen levels in nearly all of the tumours. The fully-oxygenated tumours are more easily destroyed by radiotherapy.
The drug was shown to be effective in a wide range of cancers, including lung, bowel, brain, and head and neck cancer. This older medicine is no longer patented and is readily and cheaply available from generic medicines manufacturers.
Lead author, Professor Gillies McKenna, at the Cancer Research UK/Medical Research Council Institute for Radiation Oncology in Oxford, said: “This is an exciting result. We have now started a clinical trial in Oxford to see if we can show the same results in cancer patients. We hope that this existing low cost drug will mean that resistant tumours can be re-sensitised to radiotherapy. And we’re using a drug that we already know is safe.”
Dr Emma Smith, Cancer Research UK’s science information manager, said: “The types of cancer that tend to have oxygen deprived regions are often more difficult to treat – such as lung, bowel, brain and head and neck cancer. Looking at the cancer-fighting properties of existing medicines is a very important area of research where medical charities can make a big impact and is a priority for Cancer Research UK. Clinical trials will tell us whether this drug could help improve treatment options for patients with these types of tumour.”
Ashton et al., ‘The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia’. Nature Communications, 2016. doi:10.1038/ncomms12308
* Atovaquone is a drug used in both the treatment and prevention of malaria. It is usually prescribed to travellers as malarone, which is a combination of atovaquone and proguanil