Researchers from the University of Oxford have investigated the potential for the commonly used anti-malarial and pneumonia drug Atovaquone to improve lung tumour receptiveness to cancer treatments such as chemotherapy and radiotherapy.
Results from the ATOM clinical trial at the University of Oxford have shown that the anti-malarial drug Atovaquone can reduce very low oxygen tumour environments. This has the potential to make cancers behave less aggressively and to improve the impact of everyday cancer treatments.
Cancers metabolise a large amount of oxygen in order to create the energy needed to divide, grow and spread rapidly. This results in oxygen-starved, or ‘hypoxic’, environments around tumour cells.
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This proves problematic as hypoxic tumours behave more aggressively and are more resistant to most treatments, especially radiotherapy. Radiotherapy relies on oxygen to attack cancer cells, and previous studies have shown that three-times higher doses of radiation are needed to destroy tumours in hypoxic environments, compared to those in oxygen rich environments.
The ATOM study, published in Clinical Cancer Research, administered Atovaquone to patients with non-small cell lung cancer before the surgical removal of their tumours. Using state-of-the-art scans to measure tumour hypoxia, this study found that tumours had 55% less hypoxic volumes than those who didn’t receive the drug.
Following genetic analysis, it was shown that Atovaquone successfully disrupted the metabolic pathways of the tumour that are involved in the consumption of oxygen to create energy for tumour cells. The drug successfully reprogrammed the tumour cell metabolism so that more oxygen was present around the tumour, making it more susceptible to treatments.
Professor Geoff Higgins, Consultant Oncologist at the Oxford University Hospitals Trust and lead researcher of this University of Oxford project said, “Although radiotherapy is already an extremely effective treatment, there is scope to further increase its ability to cure patients. Reprogramming a cancer cell to make it more receptive is one way of doing this.”
“I’m delighted that the results from the study are so positive so that we can take the next step towards repurposing a well-established drug as a new, effective anti-cancer treatment.”
Atovaquone is a highly-promising clinical drug, as it is already in wide circulation in the prevention and treatment of malaria. As an FDA-approved drug that is cheap and has hardly any side effects, it could be quickly adopted into clinical use if shown to improve the impact of cancer treatments such as radiation therapy. Laboratory experiments have shown its effect is not lung cancer-specific and it is likely to decrease the hypoxic environment of many types of tumour and so may improve treatment outcomes for many different cancer patients.
Dr Malcolm Howat of the Howat Foundation said, “Despite being the biggest cause of death in the UK, there is still much to be learnt about cancer and how we can optimise treatment. Atovaquone’s anti-hypoxic qualities, as discovered in this study, is one part of this puzzle.”
“We are thrilled to have supported this work, and helped to translate the laboratory findings with this drug into a successful clinical trial within such a short space of time.”
Source: University of Oxford