by Australian National University

NLRC4 attenuates tumor development in Apc^min/+ mice. Credit: Nature Immunology (2024). DOI: 10.1038/s41590-024-01988-6

An immune protein could hold the key to developing new drugs to help fight bowel cancer, according to new research from The Australian National University (ANU).

Bowel cancer is the second deadliest cancer in Australia, killing more than 100 Australians every week. However, almost 99% of bowel cancer cases can be successfully treated when detected early.

In a new study published in Nature Immunology, the ANU researchers found that a cancer-blocking immune protein called NLRC4 finds cancer-causing damaged DNA and puts up scaffoldings to repair damaged DNA.

The scaffolds made by NLRC4 around the damaged DNA stop less healthy cells from growing and dividing during the repair process. This is important as it helps prevent healthy cells from turning into cancer cells or cells that are becoming cancerous from turning into a tumor.

Lead author and ANU immunologist, Professor Si Ming Man, said researchers traditionally believed that NLRC4 only kills infected cells. However, for the first time, new work at the ANU has found that this protein is also constructive.

"We found an immune protein that can build a scaffold around damaged DNA to help repair damage and prevent cancer, a bit like Bob the Builder. This protein was previously considered to be destructive—more like the Grim Reaper," he said.

"Our research shows that developing new drugs that can turn NLRC4 from the Grim Reaper into Bob the Builder can in turn help fight bowel cancer."

Bowel cancer develops when cells become abnormal due to changes in the DNA inside the cell. These are called mutations or faulty genes.

"Most mutations happen during a person's lifetime due to exposure to harmful chemicals that break and damage our DNA, but some can be inherited from our parents," study co-author Dr. Cheng Shen, also from ANU, said.

"People with a strong family history of certain cancers, like bowel cancer, can use genetic testing to see if they have cancer-causing mutations. Those people without a family history of bowel cancer should also undergo regular health checks as mutations can accumulate with age."

The ANU researchers also found that people with bowel cancer carry less NLRC4 in their body. This makes NLRC4 a promising biomarker, meaning it helps predict who will fare better or worse after being diagnosed with bowel cancer.

"Checking the amount of NLRC4 in pre-cancerous polyps could help guide the frequency of bowel cancer screening," Professor Man said. "We hope our cancer research at the ANU helps raise awareness of cancer prevention, detection, and treatment."

More information: Cheng Shen et al, Inflammasome protein scaffolds the DNA damage complex during tumor development, Nature Immunology (2024). DOI: 10.1038/s41590-024-01988-6

Journal information: Nature Immunology 

Provided by Australian National University