The team of Oncode Investigator Louis Vermeulen (Amsterdam UMC, location AMC) has used organoid technology and the application of lithium to discover how the chance of polyps forming in the intestine, and thus the development of colorectal cancer, can be reduced. Competition between stem cells in the gut plays a key role in this. The results appeared in the leading journal Nature today.
This can have a major impact, especially for patients with a hereditary form of colon cancer (Familiar Adenomatous Polyposis or FAP).
Stem cells in the gut are located in the so-called crypts and are responsible for the formation of different cell types that are necessary for the renewal of the gut lining. This process is essential for a healthy gut. “During this process, spontaneous mutations can arise, for example in the APC gene,” says Oncode Investigator Louis Vermeulen. “These mutations can cause polyps to form in the gut, a precursor to colon cancer.”
When a stem cell acquires an APC mutation, competition arises between the healthy and mutant stem cells in a crypt. Researchers at the Vermeulen lab have now shown for the first time that these cells are in so-called 'super-competition' with each other. “Using organoid technology, we discovered that mutant cells actively suppress the growth of healthy cells,” first author Sanne van Neerven explains. “We then investigated whether we could suppress this negative effect. It turned out that we could boost the healthy cells by treating them with lithium. This resulted in fewer polyps, which in turn reduces the risk of developing colon cancer.”
Lithium has been used for many years for patients with a bipolar disorder, so there is extensive experience with this drug. Last month, Vermeulen and Van Neerven received a large grant from the Dutch Cancer Society (KWF) to investigate whether lithium can inhibit the development of cancer in FAP patients who carry this dangerous mutation.