Completed Cancer Genetics & Molecular Biology

Molecular Determinants of Radiosensitivity

Funder MRC (part of UKRI)
Recipient organisation
Funding £1.7M
Period Mar 2017 — Sept 2019

In plain English

AI plain-English summary

Around 40% of cancer patients receive radiotherapy, but the dose is limited by damage to healthy tissue, leaving some tumours untouched. This research tackles two reasons radiotherapy fails. First, tumour cells have internal proteins that help them survive radiation. The team has identified these proteins and shown that blocking them makes tumour cells far more vulnerable to radiation, while healthy cells remain unharmed. Second, tumours often have oxygen-starved cores where radiation is much less effective. The researchers found that an existing anti-malarial drug can reduce oxygen consumption by cancer cells, boosting oxygen levels in those resistant regions. They have already demonstrated this works in mice and are now running a clinical trial to see if the drug improves oxygen levels in human tumours. If the drug and protein inhibitors prove effective, radiotherapy could become more powerful against a wider range of cancers without increasing side effects. That would mean better tumour control for the many patients who currently receive sub-lethal doses. The clinical trial is the critical next step—if it confirms the oxygen-boosting effect, the drug could be rapidly repurposed, since its safety profile is already known.

View original technical description
Radiotherapy uses radiation to kill tumour cells and is given to about 40% of cancer patients as part of their treatment. There is a maximum radiation dose that can be given to a patient because radiation also damages the healthy tissues that surround the tumour. This radiation dose may thus not be sufficient to kill the tumour. The aim of our research is to improve radiotherapy by making tumour cells more sensitive to radiation. We have identified particular proteins that are important for a tumour cell to survive radiation. We showed that when these proteins are inhibited, the radiation kills tumour cells more effectively without affecting healthy cells. The outcome of radiotherapy is also influenced by the tumour environment. Tumours often have core areas with low oxygen levels. As the absence of oxygen greatly decreases the efficacy of radiation, these regions are much more resistant to radiotherapy. One way to improve the availability of oxygen in these areas is to reduce the amount of oxygen that is consumed by cancer cells throughout the tumour. We have identified an anti-malarial drug that can do exactly that and showed that it improves radiotherapy in mice. We are now conducting a clinical trial to test whether this drug improves oxygen levels in patients’ tumours.

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Researchers

Amato Giaccia (Principal Investigator)W Gillies McKenna (Principal Investigator)

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Original classification

Intramural

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