Researchers have solved a long-standing mystery about why physical force slows cancer growth. The answer could change the way cancer is treated.
A multidisciplinary team from University of Galway CÚRAM, Taighde Éireann-Research Ireland Center for Medical Devices and the University of Leuven in Belgium built an innovative AI-accelerated computational model to test the theory.
The findings suggest that learning how to harness the pressure of physical forces against tumors could open up a whole new role for treatments known as mechanotherapy in the fight against cancer.
This study Proceedings of the National Academy of Sciences at https://www.pnas.org/doi/10.1073/pnas.2523159123
Dr. Irish Senthilkumar, postdoctoral researcher and leader of the study, said: “Cancer cells are known to evade many of the body’s normal growth controls, but tumors still respond to mechanical pressure. Until now, we didn’t understand why this happens. So our aim was to investigate the underlying mechanisms at the cellular level.”
Dr Eoin McEvoy, Senior Research Scientist at CÚRAM and Associate Professor of Biomedical Engineering at the University of Galway, said: “This research has important implications for improving drug response and designing new mechanotherapy treatment regimens as we gain a better understanding of how cell compaction and compaction affect things like drug penetration and efficacy.”
The study highlights what scientists have known for decades: tumor cells seem to respond to one thing that can’t be easily reversed with chemicals: physical pressure. In other words, applying enough physical pressure to a tumor slows its growth. However, the reason was not completely understood.
The key lies in how cells grow in the first place. Before a cell can divide, it must grow larger. This is done by manufacturing complex biomolecules (proteins, lipids, and other building blocks) that draw water into cells through osmotic pressure, causing them to expand like little balloons. When a cell reaches a critical size, it can divide into two. Under normal circumstances, this expansion process works smoothly. But something interferes with that process when the tumor becomes physically trapped by surrounding tissue compressing it. External mechanical loads create high hydrostatic pressures that counteract osmotic expansion from within. result? Cells are no longer able to reach the size necessary to cause division. Growth stagnates. In other words, the physical structure of the tumor is not just a passive background, but an active participant in the disease.
Dr McEvoy added: “The implications go far beyond explaining interesting biological processes. Many anti-cancer drugs work by targeting cell division. If the tumor’s mechanical environment already suppresses growth, understanding that interaction could reveal why some drugs work better in certain tumor types or locations and others don’t.”
The AI-accelerated computational model developed by the research team performs complex calculations to simulate how thousands of individual cells collectively grow and reorganize under the pressure of mechanical stress and lack of room to grow. Without an AI model, simulations would be incredibly slow.
The researchers tested the model’s predictions against real-world laboratory experiments using breast cancer spheroids, small ball-shaped clumps of cancer cells grown in 3D culture that closely mimic how tumors behave in the body.
The results showed that the predictions matched experimental results, giving the scientists confidence that they had identified the underlying mechanism of how pressure slows cancer growth.
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Reference magazines:
Senthilkumar, I. and others. (2026) Stress-dependent proliferation in breast cancer results from mechanosmotic coupling and cell sizing checkpoints. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.2523159123. https://www.pnas.org/doi/10.1073/pnas.2523159123
