An international team of scientists has identified key factors underpinning the development of bowel or colorectal cancer in patients with a genetic predisposition to the disease.
The study, led by researchers at the Cancer Research UK Beatson Institute at the University of Glasgow, and the University of Helsinki, and published in Nature, provides crucial insight into the early stages of the disease, and also identifies a molecule that’s a ‘key player’ in this process, which could lead to new ways to prevent tumour development in high-risk individuals.
The study, performed in mouse models, looked at APC, one of the most commonly mutated genes in colorectal tumours, to identify how APC mutant cells compete with neighbouring normal cells. The researchers discovered the involvement of a molecule called NOTUM in the development of the disease. They hope that one day it will be possible to deploy NOTUM inhibitors, some of which are currently under development, as a possible early treatment.
Professor Owen Sansom, co-investigator of the Cancer Research UK Grand Challenge SPECIFICANCER team and Director of the Cancer Research UK Beatson Institute, Glasgow said: “We’ve known for a few years that APC loss gives cells a competitive advantage over their non-mutant neighbours, making them very good at forming cancer in the gut. With this study, we’ve used model systems to uncover what causes APC-mutant cells to become super-competitors and drive the very early stages of colorectal cancer.”
The researchers believe that pinpointing the involvement of the molecule NOTUM in these early stages of colorectal cancer could be the key to preventing the disease in high-risk individuals, such as those with familial adenomatous polyposis (FAP), who inherit a defective copy of APC.
