Personalized Treatment for Colon Cancer Considered

Researchers from UNC Lineberger Comprehensive Cancer Center have discovered a potential personalized treatment for colorectal cancer patients with low levels of the NLRX1 protein.

Prior studies have shown that NLRX1 plays a role in regulating immune system signals to prevent hyperactive inflammatory responses by downregulating signals that help trigger a wider immune response.

In the current study, published in Cell Reports, researchers discovered that several laboratory models of colorectal cancer and human tissue had markedly low levels of NLRX1.

“What we're proposing is, if you can profile people with low NLRX1 in their colorectal cancer, you could consider using this therapy that we identified,” said senior author Jenny P. Ting, PhD. “We have identified a critical biomarker for this disease.”

During the study, researchers analyzed the effects of deleting NLRX1 in preclinical models of sporadically-growing colorectal cancer.

The results of the study showed that within an animal model that contained mutations in the adenomatous polyposis coli (APC) gene, approximately 80% of human colon tumors had a mutation in the APC gene.

The APC mutation has been known to lead to the spontaneous growth of colon cancer tumors. The deletion of NLRX1 showed a significant increase in tumor growth and in the activation of signaling pathways that drive cancer.

Furthermore, there was a lower expression of NLRX1 in the human cancer cell samples than the normal cells. Additionally, numerous public databases of colon cancer samples were examined and demonstrated a decreased expression of NLRX1.

Since researchers know NLRX1 limits the activation of signals that trigger other cancer drivers, they believe their findings can have treatment implications.

Additionally, researchers tested a drug used for arthritis that blocks one of the downstream pathways normally down-regulated by NLRX1. The results demonstrated the drug that blocks the small signaling protein IL-6, decreased tumor growth and activation of downstream cancer-driving signals.

These findings suggest that IL-6 blockers have the potential to redirect against colorectal cancers with low levels of NLRX1.

“We're arguing that clinicians could analyze NLRX1 expression, and provide them with a more targeted treatment based on that finding,” said first study author Alicia A. Koblansky PhD. “We want to help clinicians to drive precision medicine for patients as much as possible.”