Bowel Cancer: Hope Rises For Life-Saving Treatment

Experts have uncovered a ‘big bang’ moment which determines how bowel cancer will grow, new landmark research reveals.

According to the discovery, published  in medical journal Nature, the crucial moment occurs when bowel cancer cells hide themselves from the immune system in a process called immune escape.

This enables the cells to interfere with genes that normally allow the cancer to be detected by the body’s first line of defense, the immune system.

After the point of immune escape, the experts observed that very few changes occur in how the cancer presents itself, making it more difficult to treat.

The researchers hope this discovery will help doctors identify patients who are more likely to respond to immunotherapy—a treatment that helps the immune system fight cancer—including vaccines for the disease.

‘Some bowel cancers are “born to be bad”,’ Professor Trevor Graham, director of the Centre for Evolution and Cancer at The Institute of Cancer Research, explained.

‘How they interact with the immune system is set early on. Our research suggests that a bowel cancer’s relationship with the immune system doesn’t change very much as it grows.

‘If we can target that relationship early on, treatment should have a stronger chance of success.

The Big Bang” moment occurs when bowel cancer cells successfully hide themselves from the immune system

As the only form of the disease that is solely surging in under 50s, experts are desperate to better understand how tumours evolve and change over time, so they can treat the disease earlier and offer patients a better prognosis.

A number of factors are thought to be behind the rise, such as an increase in screening and testing, diets high in ultra-processed foods, and even antibiotic use, but no smoking gun has yet been found.

There are around 44,100 new cases of bowel cancer diagnosed every year in the UK, and 142,000 in the US, making it the fourth most common cancer in both countries.

Treatment depends on whether the cancer started in the large bowel, known as colon cancer, or the rectum, but patients are usually offered a combination of treatments including surgery, chemotherapy, radiotherapy and targeted medicines.

Just 15 per cent of bowel cancers are thought to respond well to immunotherapy—which is sometimes used to treat advanced bowel cancer that has spread to other parts of the body— with the remainder less likely to respond to this type of treatment.

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In the study, scientists at The Institute of Cancer Research, Fondazione Hum

But now, with this new discovery experts hope that they will be able to change the course of the disease, and offer more personalised treatment plans.

‘As bowel cancer treatment becomes increasingly personalised, understanding how tumours evolve and change matters even more than it did before,’ Prof Graham explained.

‘Like the explosion which set the course of the universe, bowel cancer’s Big Bang gives us the biggest clues of what its future holds and how we might change that future.’an Technopole and Chalmers University of Technology analysed how immune and cancer cells behaved in 29 bowel cancer patients.

Specifically, they looked at how these cells controlled gene activity without changing the DNA sequence, known as epigenetics.

They found that cancer cells can escape the immune system by altering how DNA is ‘read’ to make RNA, the instructions used to make proteins that attract immune cells.

By minimising the number of these red flag proteins, called neoantigens, appear on the surface of a cancer cell, these changes make it harder for the immune system to recognise and destroy the cancer.

The researchers believe that combining traditional immunotherapy with epigenome-modifying drugs could make existing treatments more effective, encouraging the cancer to produce more neoantigens for the immune system to target.

Several bowel cancer vaccines are currently in clinical trials, which oncologists hope will be able to train the immune system to prevent bowel cancer from coming back after initial treatment by detecting and destroying newly emerging cancer cells.

Professor Eszter Lakatos, a mathematical biologist at Chalmers University of Technology and the University of Gothenburg, Sweden, and study lead author, said: ‘Our research group has investigated and found answers to how cancer cells render themselves invisible to the immune system.

Dame Deborah James, nicknamed the ‘bowel babe’ raised more than £11.3mn for Cancer Research and is credited for increasing awareness of the disease, which killed her in 2022 aged 40

‘Our hope is that these insights will eventually lead to more targeted, effective and early treatments in addition to surgery.’

Symptoms often include changes in bowel movements, such as constipation or diarrhoea, needing to go with more urgency, blood in the stool which may look red or black, abdominal pain, bloating, fatigue and unexplained weight loss.

Anyone experiencing these symptoms is encouraged to contact their GP for advice.

But because symptoms such as bloating, abdominal cramps and fatigue can overlap with less serious health issues, such as period pain, bowel cancer is not always caught in its first stages.

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Dr Catherine Elliot, Director of Research at Cancer Research UK, said: ‘To beat bowel cancer for everyone, we need to understand what happens at the very earliest stages of the disease.

‘No matter how different bowel cancer tumours can look, one defining moment at the start makes a big difference to how the cancer grows.’

She continued: ‘Bowel cancer has an insidious ability to resist treatment. Immunotherapy is starting to work well for patients, but it doesn’t work for everyone.

‘This research helps us understand why, as well as giving us new insights to make immunotherapy work better for bowel cancer.’

Tom Collins, the Research Lead for Discovery Research at the Wellcome Trust, added: ‘Through tracing the earliest stages of bowel cancer, the research team has shed valuable new light on a mechanism that could lead to more targeted, effective and early treatments.’

‘This is a powerful example of discovery science. Research at this molecular level has provided a deeper understanding of how bowel cancer develops, which could lead to the improved health outcomes for patients in the long-term.’

culled from Daily Mail