Innovative DNA Approach May Overcome Immunotherapy Resistance in Colorectal Cancer

A research team from the University of Alberta has made a promising discovery that could enhance the effectiveness of immunotherapy for colorectal cancer, a disease that often resists current treatments. Approximately 80% of colorectal cancers do not respond to existing immunotherapies because they fail to activate a critical immune protein called STING (stimulator of interferon genes). This protein is essential for triggering the body's immune response against tumors. The team identified a specific DNA structure capable of activating STING in resistant cancer cells, opening new avenues for therapy.

Principal investigator Kristi Baker explains that by combining immunotherapies with these specially designed DNA molecules, it may be possible to induce a much stronger immune attack against stubborn cancer cells. Their research, published in Cell Reports, involved experiments on cell cultures, animal models, and human tumor organoids, revealing that highly repetitive DNA regions can activate STING.

First author Shayla Mosley, a Ph.D. candidate, stated that introducing these DNA structures into poorly immunogenic tumors significantly improved STING activation and prompted the formation of cytotoxic T cells capable of killing tumor cells. This approach suggests a potential method to bolster immune responses where current treatments fail.

The study also highlights that radiation and some chemotherapies, which increase the presence of STING-activating DNA, could be combined with this strategy to enhance outcomes. By staying ahead of tumor adaptation, this research aims to create more durable and effective treatments. The team is now further exploring other DNA structures using atomic force microscopy to identify additional candidates.

This research holds significance not only for colorectal cancer patients—who face a high mortality rate—but also offers insights into addressing resistance to immunotherapy across other cancers and diseases involving immune system dysfunction. The work underscores the importance of understanding the molecular mechanisms underlying immune activation and paves the way for innovative combination therapies.

Source: https://medicalxpress.com/news/2025-06-colorectal-cancers-resist-immunotherapy-dna.html