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Immunotherapy hope for bowel cancer patients

Tuesday July 9th, 2019

Immunotherapy could benefit people who have stopped responding to a bowel cancer drug, according to a major new study.

Scientists at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust have discovered that bowel tumours that had initially responded to cetuximab before developing resistance became more visible to the immune system. This leaves them potentially vulnerable to immunotherapies.

They hope their study – described as “enormously exciting” – could lead to new approaches to treatment and also to tests that could assess which patients are likely to develop resistance to cetuximab most rapidly.

The research, which is published in the latest edition of Cancer Cell, involved the examination of tumour samples from 35 people with advanced bowel cancer, all of whom were treated as part of a clinical trial of cetuximab that was led by the ICR and The Royal Marsden.

Cetuximab is effective for some people with advanced bowel cancer – but the treatment only works in around half of patients, and most will eventually stop responding as their cancer becomes drug resistant.

Although the researchers found that genetic changes that could only explain the development of drug resistance in 36% of the tumours they studied, in five out of seven patients who had stopped responding to cetuximab, tumours had become heavily infiltrated by non-cancerous cells from supportive tissue around the tumour. This nurtured the cancer cells and helped them to grow during treatment.

When the team went on to study the different types of immune cells in tumour samples before and after treatment with cetuximab, they found that on average, cancer-killing immune cells were six times more active in tumours that had become resistant to cetuximab than those that had not responded to the drug from the outset.

They believe that cetuximab kills cancer cells by sending signals that attract immune cells to the tumour. Immunotherapies designed to take the brakes off the immune system could be effective in these cancers.

Researchers at the ICR and The Royal Marsden have now begun a phase II clinical trial of a combination of two immunotherapy drugs, nivolumab and relatlimab, in patients with advanced bowel cancer whose tumours have stopped responding to a combination of cetuximab and chemotherapy.

Dr Marco Gerlinger, team leader in translational oncogenomics at The Institute of Cancer Research, London, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, said: “In our new study, we have shone a light on the complex biology that lies behind the ability of bowel cancers to evade treatment with the targeted drug, cetuximab.

“Most bowel cancers are ‘immune deserts’ – so it’s enormously exciting to see that cetuximab attracts immune cells into these tumours.”

Professor David Cunningham, Director of the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, added: “This finding could have implications for the treatments we provide to patients with this disease.”

Cancer Cell 8 July 2019

Tags: Cancer | Gastroenterology | Pharmaceuticals | UK News

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