Hope for colorectal cancer drug

Wednesday October 18th, 2017

Scientists have identified a new way of modifying the Wnt cell signalling pathway that could help treat colorectal cancers, it has been announced.

Laura Novellasdemunt of the Francis Crick Institute, London, UK, and colleagues explain that the tumour suppressor gene APC is mutated in most colorectal cancers, leading to Wnt activation.

They took a closer look at how the APC mutation affects Wnt activation using the gene-editing tool CRISPR. They found that the area of the APC gene called the beta-catenin inhibitory domain is affected by pathological levels of Wnt activation.

When the beta-catenin inhibitory domain is deleted, beta-catenin removes proteins to inhibit Wnt activation, using an enzyme called USP7. This drives tumour growth, they explain in yesterday's (17 October) Cell Reports.

They write: "The Wnt-activating role of USP7 is specific to APC mutations; thus, it can be used as a tumour-specific therapeutic target for most colorectal cancers."

The team believes this new drug target would be specific to tumour cells and less toxic than current treatments, which cause side-effects because Wnt signalling is vital for the functioning of many organs.

Ms Novellasdemunt says: "There has long been a need to find more effective and less toxic drugs to treat bowel cancer. We have found a novel drug target that could provide the basis for a better therapy in patients in the future."

Senior author Dr Vivian Li added: "Current treatment for bowel cancer is mostly generic, while targeted therapy will help future development of personalised medicine. The protein that we've identified holds great promise as a therapeutic target for bowel cancer treatment."

Novellasdemunt, L. USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating beta-catenin deubiquitination. Cell Reports 17 October 2017; doi: 10.1016/j.celrep.2017.09.072 [abstract]

Tags: Cancer | Gastroenterology | Pharmaceuticals | UK News

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