Drug discovery for bowel cancer prevention and treatment
Lead researcher: Dr Nagore De Leon
Location: University of Oxford
Grant award: £25,000
Dr De Leon looked for new drugs to stop bowel polyps from progressing into cancer.
The challenge
Almost all bowel cancers develop from a precancerous polyp (a growth in the bowel that isn’t cancer, but can turn into cancer). This stage is a key opportunity for intervention to prevent bowel cancer before it starts.
Some people have an inherited condition that causes them to have lots of polyps. While these can be removed in a colonoscopy, this is invasive and so can be difficult for patients. There’s also a risk that new polyps will form and progress to cancer between colonoscopies. Other ways to prevent bowel cancer are needed.
The science behind the project
Changes (mutations) in something called the BMP signalling pathway inside our cells can change how cells grow, causing them to do this in the wrong way. This means they can develop into cancer.
Some inherited conditions, like Hereditary Mixed Polyposis Syndrome, are caused by these mutations. Patients with these conditions can get many polyps which can then become cancerous. This means they’re more at risk of developing bowel cancer.
Dr De Leon’s project tested drugs which target parts of that BMP signalling pathway. By targeting these parts of the pathway, they could stop the polyps developing into cancer.
The drugs were tested on miniguts - tiny 3D models of the bowel grown in the lab - to see if any of them targeted the right bits of the pathway.
Results
Almost 1,500 drugs were tested on the miniguts. Dr De Leon compared their effect on normal bowel tissue and bowel tissue with mutations in the BMP signalling pathway.
A series of steps to find the best candidates whittled this list down to a final set of 27 drugs which show the most promise.
What happens next?
Dr De Leon is planning further work to investigate these 27 drugs to understand the mechanisms of how they might affect polyp development. She will also be collecting data on safety and dosage - important steps on the way to a clinical trial.
Finding a drug which can help prevent bowel cancer would have a large impact on both patients and the health service. Being able to take a drug which stops polyps from becoming cancer would reduce the reliance on colonoscopies to remove them.
The main benefits would be to those with a high risk of bowel cancer due to inherited genetic conditions affecting their BMP signalling. Depending on how any particular drug works, it might also be effective for other syndromes which increase the risk of bowel cancer. Possibly, it could even help people who are at high risk of bowel cancer for other reasons, or who already have polyps.
This project funded in partnership with Never Too Young.
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