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 is looking for new drugs to stop bowel polyps from progressing into cancer. 

The challenge 

Almost all bowel cancers develop from a precancerous polyp (non-cancerous growths), and so this stage is a key target for intervention before the growth becomes cancerous.

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 always 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 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 and colleagues will be testing drugs which target parts of that BMP signalling pathway. By targeting these parts of the pathway, they could stop the polyps developing into cancer. They’ve already shown that in mice this works, reducing the number of polyps developed and preventing bowel cancer. 

The next stage is to see how to do this safely in humans. Dr De Leon and colleagues will be using innovative “3D minigut models”. By growing small sections of bowel from existing bowel cells, they’ll test lots of different drugs. This will show if any of them target the right bits of the pathway. They’ll also be checking to see if the drugs stop the growth of the ‘dangerous’ cells which could become cancer, but leave the healthy cells alone. 

What difference will this project make? 

Discovering 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 don’t have a genetic condition but are a high risk of bowel cancer for other reasons, or those who already have polyps developing. 

• For more information see our announcement of the grant
  

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This project funded in partnership with Never Too Young.