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Could Gut Stem Cells Hold the Key to Preventing Bowel Cancer?
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Previous studies indicate that stem cells play an important part in cancer development, however, therapeutically targeting these cells in established tumors has proved challenging.
New research presented at the 2018 NCRI Cancer Conference proposes that by treating pre-cancerous stem cells with existing cancer therapeutics at an early stage, it may be possible to prevent bowel cancer – in those with a high risk of the disease.
Michael Hodder from the Cancer Research UK Beatson Institute, Glasgow, UK commented in a recent press release: "Stem cells play an important role in our bodies because they are capable of dividing and growing into lots of different types of cells. They are also found in tumors where this ability to multiply makes it more difficult to stop cancers from growing and spreading.”
"I wanted to study cancer stem cells more closely to see if I could discover a vulnerability that could be targeted to treat cancer more successfully."
The researchers studied the role of gut stem cells using a mouse model of familial adenomatous polyposis or (FAP).
What is familial adenomatous polyposis?
Familial adenomatous polyposis is a rare, inherited condition that is characterized by cancer of the colon and rectum. Multiple non-cancerous growths (polyps) can begin to develop early on (teenage years) in those with ‘classic’ FAP, if these polyps are not removed, they eventually become malignant. Attenuated FAP (a variant of the disorder) also exists, in this case polyp formation is delayed. The average age of colorectal cancer onset for attenuated FAP is 55 years, compared to 39 years for those with classic FAP.
Both classic and attenuated familial adenomatous polyposis are caused by mutations in the adenomatous polyposis coli ( APC ) gene.
The mice used in the study possessed a faulty APC gene equivalent, meaning that if they remained untreated, they would develop tumors in their gut. To determine whether it may be possible to stop tumors from developing in the animals, the team administered existing cancer therapeutics at a very early stage. One in particular, cisplatin , a platinum-based chemotherapy drug, showed promise – preventing cancer from developing in the mouse model.
The team also investigated the sensitivity of cisplatin in both pre-cancerous stem cells and ‘normal’ stem cells. Pre-cancerous stem cells in the mouse gut had a greater sensitivity to cisplatin, suggesting that it could be possible to prevent bowel cancer if the ‘right’ cells are treated early enough – before the tumor has developed.
"This research is in mice, not in humans, but it does present the possibility that targeting stem cells could be a route to preventing tumors in people with a very high risk of bowel cancer.” said Hodder.
"Cisplatin is a powerful cancer drug that can cause serious side effects, so we will need to discover whether it can work on pre-cancerous stem cells at very low doses, or whether we can find other drugs that have the same effect but with fewer side effects."
The team are now exploring several other drugs to determine whether there may be an alternative drug that possesses similar efficacy to cisplatin – but with an improved toxicity profile.
