AN INTERNATIONAL team of scientists have identified key factors underpinning the development of bowel cancer in patients with a genetic predisposition to the disease.
The research published today 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.
This is information which could lead to new ways to prevent tumour development in high-risk individuals.
The study 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, 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.”
Dustin Flanagan, co-lead on the study, added: “Rather than targeting the APC-mutant cells, our strategy has been to bolster the fitness of the surrounding normal cells by inhibiting NOTUM.
“By removing the suppressive effect NOTUM has on neighbouring cells, Apc-mutants lose their competitive edge and it becomes a fairer fight, slowing or even preventing tumour growth.”
The study is the result of a collaboration with colleagues at the Alzheimer’s Research UK Drug Discovery Institute at University College London.