Psychiatric drug could prevent bowel cancer

Thursday June 3rd 2021

A clinical trial is to begin on whether a commonly used drug for psychiatric disorders can be used to prevent bowel cancer.

It follows a study by researchers in the Netherlands that showed how Lithium can boost the fitness of healthy cells in the gut, which prevents the development of the disease.

The trial is to recruit patients with familial adenomatous polyposis (FAP), a genetic mutation, which means they are almost certain to develop bowel cancer in their lifetime, unless the entire large bowel is removed.

It is believed most bowel cancer cases are caused by mutations in the APC gene, which have a competitive advantage over their healthy counterparts, which leads to unrestricted growth and cancer.

It was unclear how the mutant stem cells become dominant, but new research, published in the latest edition of Nature, reveals they actively emit signals that sabotage the function of healthy stem cells in the gut.

Senior author Professor Louis Vermeulen, group leader at the Centre for Experimental Molecular Medicine at Amsterdam UMC, said: “We have uncovered the very first steps in the development of bowel cancer. We found that following the occurrence of a mutation in a key gene that regulates stem cells in the intestine, these cells turn into cheaters that actively suppress the normal cells in the environment.

“This is a totally new concept as it was always thought that mutant cells that can turn into cancer simply proliferate faster or are resistant to cell death. But our findings indicate that cells on their way to a full malignancy can actively suppress the stem cells in the vicinity to gain a competitive edge. This is a concept we refer to as supercompetition.”

The Dutch Cancer Society (KWF) is now funding a trial that will test lithium in bowel cancer development in individuals with FAP, who have mutations in their APC gene and develop hundreds of non-cancerous polyps and adenomas in their bowel.

Without treatment almost all will develop bowel cancer between the ages of 35 and 45.

The 18-month trial will recruit 10 young adult patients with FAP and researchers will collect evidence on the preventive effect of lithium on mutant stem cells and polyp formation, as well as test the safety profile of lithium.

Dr Helen Rippon, chief executive at Worldwide Cancer Research, which funded the initial research, said: “The discoveries made by Professor Vermeulen and his team are a huge breakthrough in our understanding of how bowel cancer develops. It's amazing to see innovative research like this go from the lab to the clinic as it shows just how important early-stage discovery research is to starting new cancer cures. We are all very excited to see the results from this clinical trial and the future impact these findings might have on other people with inherited cancer syndromes.”

van Neerven SM, de Groot NE, Nijman LE et al. Apc-mutant cells act as supercompetitors in intestinal tumour initiation. Nature 2 June 2021.

Tags: Cancer | Europe | Internal Medicine | Pharmaceuticals

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