Innovative RNA-Based Approach Targets CNNM4 Protein to Combat Rare and Aggressive Liver Cancer
A novel RNA-based therapy targeting CNNM4 protein shows promise in slowing the progression of aggressive liver cancer, opening new avenues for personalized treatment.
A groundbreaking international study led by Dr. Malu Martínez-Chantar at CIC bioGUNE has identified a promising new therapeutic target for cholangiocarcinoma (CCA), a rare but highly aggressive form of liver cancer with limited treatment options. The research, recently published in the journal Gut, highlights the potential of blocking the CNNM4 protein using advanced RNA technology to slow tumor growth and improve treatment responses.
Cholangiocarcinoma is frequently diagnosed at a late stage and proves resistant to conventional therapies. Only a small fraction of patients are eligible for surgery, and even after removal, survival rates remain low. This urgent need for innovative therapies prompted researchers to explore the molecular mechanisms underlying the disease.
The study found that the CNNM4 protein, which plays a role in transporting magnesium inside cells, is overexpressed in cholangiocarcinoma tissues. The research demonstrated that silencing CNNM4 effectively hampers tumor progression, decreases chemotherapy resistance, and prevents the spread of tumor cells. Restoring magnesium balance through this pathway activates ferroptosis—a natural process that selectively destroys cancer cells—while also making them more sensitive to treatment.
To achieve targeted therapy, scientists employed GalNAc siRNA technology, facilitating highly specific drug delivery to the liver. This approach enhances the safety and efficacy of treatment, representing a significant step toward personalized medicine.
Dr. Martínez-Chantar explained, "Our findings not only reveal a promising therapeutic pathway but also underscore the potential of combining molecular biology with innovative drug delivery systems to develop effective treatments for cholangiocarcinoma."
Further insights from the study reveal that targeting metabolic vulnerabilities in cancer cells can serve as a powerful strategy in disease management. Dr. Naroa Goikoetxea, a co–first author, emphasized the significance of these results in advancing targeted therapies for complex cancers.
Overall, this research exemplifies how international collaboration and scientific innovation can lead to new hope for patients suffering from this deadly cancer. As part of broader initiatives like the COST Action CA22125 Precision-BTC Network, these findings pave the way for future clinical applications and personalized treatment options for cholangiocarcinoma.
Source: https://medicalxpress.com/news/2025-09-blocking-cnnm4-protein-rna-technology.html
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