Gene Knockout Supported Tumor Eradication in Preclinical Colon Cancer Models

New University of Calgary research reveals that eliminating a single gene improves immunotherapy for colorectal cancer - a fundamental breakthrough.

The Canadian Cancer Society lists colorectal cancer to be the fourth most diagnosed cancer in Canada, and the third leading cause of death from cancer in both men and women. It is also estimated that 25,300 Canadians will be diagnosed with it, representing 10 per cent of all new cancer cases this year. In people below the age of 50, the incidence of new colorectal cases is on the rise. 

“Lots of screening programs are targeted towards catching early stage tumours in older populations, making it hard to find solutions for young patients who are typically diagnosed with an advanced disease,” says Dr. Arshad Ayyaz, PhD, an assistant professor in the Department of Biological Sciences and a member of the Arnie Charbonneau Cancer Institute.

“We still don’t know why more and more people in younger demographics are getting colon cancer, but, in many of their cases, the disease is only detected after it has spread to other tissues and organs. At these stages, the disease is harder to treat, and patient survival is much lower.”

“We’ve been able to remove the ‘invisibility cloak’ that colon cancers use to hide from treatment,” says Ayyaz, who has dedicated 20 years to researching the gut.

Immunotherapy trains a patient’s own immune system to recognize and attack tumours, reducing or removing the need for radiation and chemotherapy. Immunotherapy has yielded great results for several other types of cancer, but not colon cancer.

“Only about 15 per cent of colon cancers respond to immunotherapy,” Ayyaz says. “We performed a genetic analysis of them against those that don’t.”

What the research uncovered was a new type of cancer cell.

“The treatment-resistant tumours secrete a protein that confuses your immune system into thinking everything’s fine. It’s like an invisibility cloak,” he says. “So, we thought, what happens if we prevent the tumours from making this protein?”

The experiment involved making gene-edited versions of those cancer cells. When the gene that coded the particular protein was knocked out, it made those cells visible to the immune system.

The result was 100 per cent eradication of tumours when paired with immunotherapy treatment in mouse models.

“I couldn’t believe it at first,” Ayyaz notes. By just knocking out one gene, the results are black and white.

“Even without the immunotherapy treatments, the tumours shrank, meaning they can’t hide from the body’s natural immune response anymore.”

Ayyaz says it is very fundamental research that is still quite some distance away from clinical settings. However, the findings might be applicable to other types of cancer.

“Immunotherapy is generally ineffective against solid tumours, like those in pancreatic or lung cancer. It’s possible that a similar cloaking mechanism plays a role there. I’m hoping this discovery will go a long way to help us understand these cases better,” says Ayyaz.

“There’s a lot of ongoing cancer research and everyone takes a slightly different approach to it. For example, most efforts are focused on making the immune system more effective against cancers; while others, like us, are attempting to find out how cancers can hide themselves from a perfectly functional immune system. 

“Of course, we’re all working towards the same outcome in the end.”

Reference: Chua J, Kaur A, Mitchell F, et al. A tumor-intrinsic WNT-inhibitory NOTUM program drives immune resistance in microsatellite stable colorectal cancer. Cell Rep Med. 2026;7(5). doi: 10.1016/j.xcrm.2026.102776

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