Bowel cancer tumours produce a distinct set of overactive enzymes that chew through the gut’s protective barrier, and a researcher has built a miniature model of the disease from patient cells to prove that blocking those enzymes stops the damage. This matters because bowel cancer is the second leading cause of cancer death in the UK, and many cases are linked to preventable factors such as poor diet and chronic inflammation. The enzymes in question—hydrolases—are normally needed for digestion, but when they become too active they break down the bowel lining, letting gut microbes trigger the immune system in a way that promotes cancer. The researcher has already shown in a lab model that inhibiting these enzymes protects the barrier. If successful, this work could lead to new drugs that directly target the harmful hydrolase activity, and eventually to dietary strategies—such as increasing fibre intake—that naturally keep enzyme levels in check. The long-term goal is to shift the gut environment away from inflammation and toward a healthy balance, reducing both the risk of developing bowel cancer and the severity of the disease in patients.
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Bowel cancer is the second leading cause of cancer-related deaths in the UK, which is an unacceptable outcome as over half of these cases are preventable. My fellowship focuses on enzymes, which are proteins that chop up molecules. Too much chopping results in damage to the bowel that can over activate the bodies defences, our immune system. My goal is to find ways to stop these enzymes from overacting, potentially using drugs. In the long term, I will explore how diet can reduce the activity of these enzymes in the gut to promote a healthy balance. There are several risk factors for bowel cancer, such as being overweight, having a poor diet, and having a long-term inflammatory condition, like inflammatory bowel disease. In fact, eating too little fibre causes 28% of bowel cancer cases in the UK (CRUK). The reason diet is important is because it affects the health of the bowel, which is the part of the intestine where bowel cancer develops. The bowel is home to trillions of organisms that you need a microscope to see, called microbes. What we eat influences these microbes and can cause inflammation. Normally, the bowel acts as a protective barrier between our immune system and the microbes. But if this barrier gets disrupted, it can lead to inflammation against the microbes and create an environment that promotes cancer development. Hydrolytic enzymes also called hydrolase, are important for a healthy bowel and for digestion. However, when there is too much activity of these enzymes, it leads to inflammation and cancer. In the bowel, hydrolases are released from human cells and microbes into the gut space and collected by passing faeces-like content. By analysing these bowel contents from cancer patients, I have found that the tumour environment has specific profile of active hydrolases. I have also developed a micro-model of human bowel cancer made from patient cells. Using this model, I have shown that by blocking the activity of hydrolases, I protect the bowel barrier from damage caused by its contents. The main goal of my Future Leaders Fellowship is to identify the specific hydrolases that are causing this damage, determine their role in bowel cancer, and find new ways to stop them. This will involve developing new drugs and designing specific diets to inhibit these enzymes. Ultimately, my aim is to reduce the impact of colorectal cancer and improve the outcomes for patients.
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