Cancer research often reveals unexpected ways to fight disease by rethinking the cell’s environment. A new approach from the University of Cambridge suggests halting glioblastoma, the deadliest brain cancer, by freezing the very molecules that enable its spread.

Instead of killing cells outright, this strategy changes the conditions around them, turning aggressive invaders into quiet neighbors.

Glioblastoma is the most common brain cancer and one of the hardest to treat. Patients often survive less than 15 months after diagnosis, with only 15 percent living beyond five years. Surgery and radiotherapy can slow progress but rarely prevent recurrence.

Cancer cells left behind infiltrate healthy brain tissue, spreading silently through microscopic channels. Current drugs also struggle to penetrate the dense tumor mass, leaving few effective options.

Cancer uses hyaluronic acid

At the heart of this discovery is hyaluronic acid (HA), a sugar-like polymer that shapes much of the brain’s supporting structure.

Cancer cells rely on HA’s flexibility to latch onto surface receptors, especially CD44, which drives their movement. By chemically locking HA in place, scientists stripped away its flexibility. This effectively reprogrammed glioblastoma cells into dormancy, preventing them from invading new tissue.

Study co-author Melinda Duer is a professor in the Yusuf Hamied Department of Chemistry at the University of Cambridge.

“Fundamentally, hyaluronic acid molecules need to be flexible to bind to cancer cell receptors,” said Professor Duer.

“If you can stop hyaluronic acid being flexible, you can stop cancer cells from spreading. The remarkable thing is that we didn’t have to kill the cells – we simply changed their environment, and they gave up trying to escape and invade neighbouring tissue.”

Freezing flexibility stops cancer

The Cambridge study confirmed that HA’s behavior is not just about molecular size but about motion. High-molecular-weight HA, usually linked with healthy tissue, can still promote cancer invasion when diluted.

At lower concentrations, HA molecules move freely, adopting shapes that fit tightly into CD44 binding sites. This triggers powerful invasion signals.

At higher concentrations, HA molecules entangle with each other, limiting flexibility and dampening those signals.

Molecular motion and signals

Nuclear magnetic resonance spectroscopy revealed that HA’s ability to twist into specific conformations within nanoseconds determines whether it binds strongly to CD44.

When flexible, HA activates pathways that push cells to migrate. When immobilized, HA blocks these signals.

This explains why swelling in the brain after surgery, which dilutes HA, can encourage cancer to return at the surgical site.

Protein responses to hyaluronic acid

Proteomic analysis of glioblastoma cells highlighted how HA concentration reshapes their internal machinery.

In flexible environments, cells developed star-shaped structures and invasive protrusions, supported by actin-bundling proteins and enzymes that degrade tissue.

In stiffer environments, those invasive proteins disappeared. Instead, cells activated survival pathways, entered a dormant state, and upregulated proteins linked to quiescence, including Notch-2.

This switch showed how extracellular conditions can push cancer cells either into attack mode or into stillness.

Freezing molecules stops cancer

Researchers tested this idea further by creating a chemically modified HA that crosslinks tightly into the extracellular matrix. This version lost flexibility and, when added to cell cultures, completely stopped invasion.

Cells responded in the same way as in dense HA conditions, showing altered protein expression and increased dormancy signals. This provided strong evidence that flexibility itself, not size, is the decisive factor in driving cancer spread.

The findings give a new explanation for glioblastoma’s notorious tendency to regrow after surgery. Fluid build-up, or oedema, dilutes HA at the surgical site, making it more flexible and more capable of binding CD44.

This diluted environment inadvertently encourages cancer cells to invade again. By freezing HA in place, scientists hope to counteract this effect and stop recurrence before it starts.

Freezing may help treat cancer

“This could be a real opportunity to slow glioblastoma progression,” said Duer. “And because our approach doesn’t require drugs to enter every single cancer cell, it could in principle work for many solid tumours where the surrounding matrix drives invasion.

“Cancer cells behave the way they do in part because of their environment. If you change their environment, you can change the cells.”

The work now moves into animal testing before any patient trials. Still, the implications extend beyond brain cancer. Many tumors rely on signals from their surrounding environment to spread.

By targeting flexibility in key molecules like HA, researchers may uncover a new class of treatments that turn cancer’s supportive scaffolding into a trap. Instead of chasing runaway cells, this method locks the very ground beneath them.

The study is published in the journal Royal Society Open Science.

—–

Like what you read? Subscribe to our newsletter for engaging articles, exclusive content, and the latest updates. 

Check us out on EarthSnap, a free app brought to you by Eric Ralls and Earth.com.

—–