Study unravels mystery about why physical forces slow cancer growth

Researchers have solved a long-standing mystery about why physical forces slow cancer growth – and the answer could reshape how the disease is treated.

A multidisciplinary team from University of Galway, CÚRAM, the Taighde Éireann-Research Ireland Centre for Medical Devices, and KU Leuven in Belgium built an innovative AI accelerated computational model to test the theory.

The research findings suggest that learning to harness the pressure of physical force on a tumor could open an entirely new role for treatments known as mechanotherapies in the fight against cancer.

The study was published in Proceedings of the National Academy of Sciences at https://www.pnas.org/doi/10.1073/pnas.2523159123

Dr Irish Senthilkumar, postdoctoral researcher and a lead on the study, said: "Cancer cells are known to bypass many of the body's normal growth controls, but tumors still respond to mechanical pressure. Until now we haven't understood why this happens, so our aim was to investigate the underlying mechanics at a cellular level."

Dr Eóin McEvoy, senior researcher with CÚRAM and Associate Professor of Biomedical Engineering at University of Galway, said: "As we understand more about how cell compression and compaction affect things like drug penetration and efficacy, the work has important implications for improving drug responses and designing new mechanotherapy treatment regimens."

The research highlighted how, for decades, scientists have noticed that tumor cells seem to respond to one thing that chemicals cannot easily override, physical pressure - put enough physical pressure on a tumor, and its growth slows down. But the reason was not fully understood.

The key lies in how cells grow in the first place. Before a cell can divide, it has to get bigger. It does this by manufacturing complex biological molecules (proteins, lipids, and other building blocks) which draws water into the cell through osmosis, inflating it like a tiny balloon. Once the cell reaches a critical size, it can split in two. Under normal circumstances, this swelling process works smoothly. But when a tumor becomes physically confined by the surrounding tissue pressing in on it, something disrupts that process. The external mechanical load creates high hydrostatic pressure, that fights against the osmotic swelling from the inside. The result? Cells can no longer reach the size needed to trigger division. Growth stalls. In other words, the physical architecture of a tumor is not just a passive backdrop, it's an active participant in the disease.

Dr McEvoy added: "The implications stretch well beyond explaining an interesting biological process. Many cancer drugs work by targeting cell division. If a tumor's mechanical environment is already suppressing growth, understanding that interaction could reveal why some drugs work better in certain tumor types or locations, and why others fail."

The AI accelerated computational model developed by the research team runs complex calculations, simulating how thousands of individual cells collectively grow and reorganise under mechanical stress or the pressure of having no room to grow bigger. Without the AI model, simulations would be impossibly slow.

The researchers validated the model's predictions against real laboratory experiments using breast cancer spheroids - small, ball-shaped clusters of cancer cells grown in 3D cultures that closely mimic how tumors behave inside the body.

The results showed that the predictions matched the experimental results, giving the scientists confidence that they had identified the genuine mechanism underlying how pressure slows cancer growth.