Scientists may have uncovered the molecular switch that lets cancer hide in plain sight.
Could this discovery change how scientists approach cancer treatment? Laboratory results suggest it might. An international team of researchers has identified a critical biological process that helps pancreatic cancer grow and avoid detection by the immune system. When they interfered with this process in animal studies, tumors shrank dramatically.
The work uncovers a central mechanism that cancer cells use to shield themselves from immune attack. Blocking that protective pathway led to a major reduction in tumor size in laboratory animals, revealing a potential new strategy for therapy.
Study Published in Cell and Backed by Global Collaboration
The findings were published in the journal Cell. The research was led by Leonie Uhl, Amel Aziba, and Sinah Löbbert, working with colleagues from the University of Würzburg (JMU), Massachusetts Institute of Technology (USA), and Würzburg University Hospital.
The study was directed by Martin Eilers, Chair of Biochemistry and Molecular Biology at JMU, as part of the Cancer Grand Challenges KOODAC team. Funding support came from Cancer Research UK, the Children Cancer Free Foundation (Kika), and the French National Cancer Institute (INCa) through the Cancer Grand Challenges initiative. Additional support was provided by an Advanced Grant from the European Research Council awarded to Martin Eilers.
MYC: A Powerful Driver of Tumor Growth
The researchers focused on MYC, a protein long recognized as a major force in cancer biology. MYC is known as an oncoprotein because it pushes cells to divide and multiply. “In many types of tumors, this protein is one of the central drivers of cell division and thus of uncontrolled tumor growth,” explains Martin Eilers.
Yet one important mystery remained. Tumors with high MYC activity grow aggressively, but they often escape detection by the immune system. How do these fast-growing cancers avoid triggering the body’s natural defenses?
MYC’s Unexpected Second Role
The study reveals that MYC does more than activate genes that promote growth. Under stressful conditions inside rapidly expanding tumors, MYC changes its behavior. Instead of attaching to DNA, it begins binding to newly formed RNA molecules.
This shift sets off a chain reaction. Multiple MYC proteins gather into dense clusters known as multimers, forming structures that act like molecular condensates. These clusters draw in other proteins, especially the exosome complex, concentrating them in a single location within the cell.
The exosome complex then carries out a cleanup operation. It breaks down RNA-DNA hybrids, which are faulty byproducts of gene activity. Normally, these hybrids serve as strong internal warning signals, alerting the immune system that something abnormal is happening inside the cell.
How Cancer Silences Immune Alarm Signals
By organizing the removal of RNA-DNA hybrids, MYC effectively shuts off these warning signals before they can trigger an immune response. Without those signals, the immune system never receives the message that cancer is present. The tumor remains hidden from immune cells.
The team demonstrated that this stealth function depends on a specific RNA-binding region within the MYC protein. Importantly, this region is not necessary for MYC’s role in stimulating cell division, meaning the protein’s growth-promoting activity and its immune evasion function are separate at a mechanistic level.
Tumor Collapse in Animal Studies
To test the importance of this RNA-binding region, researchers engineered MYC proteins that could no longer attach to RNA. Without that ability, MYC could not recruit the exosome complex or suppress the immune alarm pathway.
The results in animal models were striking. “While pancreatic tumors with normal MYC increased in size 24-fold within 28 days, tumors with a defective MYC protein collapsed during the same period and shrank by 94 per cent – but only if the animals’ immune systems were intact,” says Martin Eilers.
This showed that once the immune system was allowed to recognize the tumor, it played a decisive role in reducing its size.
A More Precise Strategy for Cancer Therapy
The findings suggest a new direction for drug development. Attempts to completely block MYC have been challenging because the protein is also essential for normal cells. Shutting it down entirely can cause harmful side effects.
The newly identified mechanism offers a more selective option. “Instead of completely switching off MYC, future drugs could specifically inhibit only its ability to bind RNA. This would potentially leave its growth-promoting function untouched, but lift the tumor’s cloak of invisibility,” explains Eilers. In theory, this would allow the immune system to detect and attack cancer cells again.
What Still Needs to Be Learned
Despite the promising laboratory results, researchers caution that clinical applications are still years away. Scientists must next determine how immune-activating RNA-DNA hybrids exit the cell nucleus and how MYC’s RNA-binding activity affects the tumor’s surrounding environment.
Dr. David Scott, Director of Cancer Grand Challenges, emphasized the broader impact of the work: “Cancer Grand Challenges exists to support international teams like KOODAC that are pushing the boundaries of what we know about cancer. Research like this shows how uncovering the mechanisms tumors use to hide from the immune system can open up new possibilities, not only for adult cancers but also for childhood cancers that are the focus of the KOODAC team. It’s an encouraging example of how international collaboration and diverse expertise can help tackle some of the toughest challenges in cancer research.“
Reference: “MYC binding to nascent RNA suppresses innate immune signaling by R-loop-derived RNA-DNA hybrids” by Leonie Uhl, Amel Aziba, Sinah Löbbert, Timothy Russell, Bastian Krenz, Francisco Montesinos, Toshitha Kannan, Omkar R. Valanju, Christina Schülein-Völk, Tim de Martines, Michael Bolz, Daniel Fleischhauer, Giacomo Cossa, Theresa Endres, Daniel Solvie, Peter Gallant, Andreas Rosenwald, Hans M. Maric, Dimitrios Papadopoulos, Seychelle M. Vos and Martin Eilers, 22 January 2026, Cell.
DOI: 10.1016/j.cell.2025.12.019
About Cancer Grand Challenges
Launched in 2020 by Cancer Research UK and the National Cancer Institute, Cancer Grand Challenges supports international teams tackling some of the most complex problems in cancer research. These challenges cannot be solved by a single scientist, institution, or country.
With awards of up to £20m, the initiative enables researchers to cross traditional geographic and disciplinary boundaries in pursuit of faster progress against cancer.
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