Led by Professor Richard Edmondson, this project set out to define the DNA damage response defects in high grade serous ovarian cancer (HGSOC) to predict patients' response to chemotherapy and the likelihood of recurrence.
The project has now finished, and we're delighted to share the results.
| Location | University of Manchester |
| Duration | January 2018 to January 2021 |
| Funding awarded | £198,414 |
| Status | Completed |
Why was this research needed?
In normal cells, when DNA becomes damaged (for example a break in one of the DNA strands) a DNA damage response is triggered to repair it. Genetic mutations can stop this DNA damage response pathway from working properly - which can lead to the growth of tumours.
All HGSOC tumours have defects in their DNA-damage response pathways.
Before this project, Professor Edmondson showed that these defects make a difference in how tumours respond to treatments.
The new project aimed to understand more about DNA damage response defects, which could move us further towards personalised treatments.
How did it progress?
The team developed assays to test for DNA damage response defects. These are tests that can be used in the laboratory to map DNA damage response defects in samples of ovarian cancer. These assays could one day be used in the clinic to find out more about a patient's tumour and help doctors and patients make treatment decisions.
Researchers used the assays to test ovarian cancer samples. They showed that all the samples had defects, but there was a lot of variation between the tumours. Each sample displayed a slightly different pattern of the DNA damage response.
Researchers then used these patterns of the DNA damage response defects to see if they could predict outcomes in patients. Firstly, they used them to predict the response of cancer cells to chemotherapy in the laboratory. Initial findings were encouraging, showing a strong connection.
The team then used the patterns to predict the clinical outcome of each sample – again showing a very strong connection between the type of DNA damage response defect(s) and the likelihood of relapse of the disease.
These findings suggest that the pattern of DNA damage response in a tumour could be used to predict patient outcomes in a clinical setting.
What happens next?
The part of the project that Target Ovarian Cancer funded is now finished, and the team completed the aims that they set out to do. It has helped to advance our knowledge of HGSOC and raises hope for the development of more personalised and targeted treatment. However, there is more work to complete to understand how this new knowledge could benefit routine patient care.
The team has secured funding from the Wellcome Trust to extend the research into recurrent ovarian cancer. These patients would have the greatest clinical advantage for this information.
For women with recurrent ovarian cancer, response to treatment is currently unpredictable and treatments are toxic leading to unpleasant side effects. Therefore, knowing which tumours are likely to respond to treatment would allow patients most likely to gain benefit from it to proceed. With those that are not likely to respond spared from the side effects.
Find out more information about the project.
