Psychiatric drug may prevent bowel cancer, researchers say
A drug available on the NHS could boost the fitness of healthy stem cells in the gut, making them more resistant to sabotage from mutant cells that cause bowel cancer, scientists say.
The findings have led to the launch of a clinical trial aimed at finding out if the commonly used psychiatric drug lithium could be used to prevent development of the cancer.
The study will recruit patients with a genetic mutation which means that, unless their entire large bowel is removed, they are almost certain to develop the disease in their lifetime.
Bowel cancer affects more than 43,000 people each year in the UK and just over half of those diagnosed survive for 10 years or longer.
It is thought that the majority of bowel cancer cases are caused by mutations in a gene called APC.
Intestinal stem cells with mutations to the gene have been shown to have a competitive advantage over their healthy counterparts and frequently outcompete them.
This leads to unrestricted growth and cancer, researchers say.
We have uncovered the very first steps in the development of bowel cancer
Until now, it was not known how the mutant stem cells won the upper hand, but new research, published in the journal Nature, shows they actively emit signals that sabotage the function of healthy stem cells in the gut.
Professor Louis Vermeulen, group leader at the Centre for Experimental Molecular Medicine at Amsterdam UMC and senior author of the paper, 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 super-competition.”
The researchers also discovered a way to prevent the mutant stem cells from interfering with the healthy ones.
Lithium, a commonly used drug for the treatment of several psychiatric disorders, prevented the mutant stem cells from taking over and forming tumours in mice by rendering the healthy stem cells insensitive to the damaging signals.
A clinical trial funded by the Dutch Cancer Society (KWF) testing the effect of lithium on bowel cancer development in individuals with familial adenomatous polyposis (FAP) will now be carried out in the Netherlands.
FAP is a relatively uncommon genetic syndrome that affects about one in 7,000 to one in 22,000 people.
Patients have mutations in their APC gene and develop hundreds of non-cancerous polyps and adenomas in their bowel.
Without treatment nearly all of them will develop bowel cancer between the ages of 35 and 45, experts say.
The discoveries made by Professor Vermeulen and his team are a huge breakthrough in our understanding of how bowel cancer develops
Sanne van Neerven, a PhD student who conducted the research, said: “Our clinical trial may reveal that lithium can be used to prevent cancer development in FAP individuals.
“But what is also important is that this trial can establish a proof of concept that manipulating competition between mutant cells and normal cells can be manipulated in such a way that the healthy cells outcompete the mutant cells.
“This is a novel strategy for cancer prevention and could be applied to many heritable cancer syndromes involving different mutations and organs, but more research is warranted in this area.”
Dr Helen Rippon, chief executive at Worldwide Cancer Research, said: “The discoveries made by Professor Vermeulen and his team are a huge breakthrough in our understanding of how bowel cancer develops.
“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.”