Cancer Research UK says an old anti-malaria drug could be repurposed as a cancer therapy. In pre-clinical studies, this drug increases oxygen levels in tumors, making them easier to treat with radiotherapy.

cancer research uk atovaquone hypoxiaAtovaquone has been on the market since 2000 as part of an anti-malarial drug. It is also commercialized by GSK under the name Mepron for certain types of pneumonia. However, as its patent has already expired it’s also cheaply available from generic manufacturers.

This small molecule drug may now have a new role in Medicine – as a booster of radiotherapy to treat a broad range of cancers. Well, according to promising pre-clinical results obtained by Cancer Research UK.

In a work now published in Nature Communications, research shows that atovaquone has potential to stop tumors from having a low-oxygen environment (hypoxia) during radiotherapy.

hypoxia cancer atovaquone ocr reduction

Fig. 1: Effects of hypoxia in cancer cells, including increased angiogenesis and immune suppression that favor tumor growth and spread.

When a tumor has low levels of oxygen, it can more easily repair the DNA damage caused by radiotherapy – reversing the treatment’s intended effect. Ensuring a supply of oxygen reduces the ability of cancer cells to repair themselves. Besides this, hypoxic conditions also trigger the tumor to be more likely to spread (metastasis).

This is why the team of researchers went to look for FDA-approved compounds that could boost oxygen levels in cells. More specifically, they were looking for candidates which decreased the oxygen consumption rate (OCR) of cells. By inhibiting the high OCR that is typical of cancer cells, the levels of oxygen would increase.

atovaquone malaria cancer hypoxia radiotherapy

Fig. 1: Microscopy images of mice tumors, treated with atovaquone and DMSO (control). The green stain (EF5) shows reduced hypoxia conditions (less bright regions) with atovaquone treatment vs. control.

As it turns out, atovaquone fits this bill. The drug slows down the rate at which cancer cells use oxygen by targeting the mitochondria. This is the how it inhibits pathogens like malaria-causing Plasmodiumand this new research shows it also works in human cancer cells.

The drug was further tested in mice disease models of a variety of cancers – including lung, bowel, brain, and head and neck cancer. Treatment with atovaquone reduced hypoxia conditions by up to 73%. When the atovaquone-treated mice underwent radiotherapy, their tumors grew more slowly (nearly half the growth rate of tumors in untreated mice).

It’s interesting to see this kind of repurposing of a well-established drug, as it simplifies the trial process and makes getting it to market easier and cheaper.

Feature Image Credit: Pixabay
Figure 1 Credit: Palazón et al. (2012) Molecular Pathways: Hypoxia Response in Immune Cells Fighting or Promoting Cancer. Clinical Cancer Research (doi: 10.1158/1078-0432.CCR-11-1591)
Figure 2 Credit: Ashton et al. (2016) The anti-malarial atovaquone increases radiosensitivity by alleviating tumor hypoxia. Nature Communications (doi: 10.1038/ncomms12308)

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