In a Cambridge lab, a team of scientists may have found a new way to fight the most aggressive brain cancer—not by killing it, but by locking it in place.

Glioblastoma, the deadliest and most common form of brain cancer, has long confounded doctors. Even after surgical removal, the cancer almost always returns, propelled by cells that slip through the brain like ghosts. But now, researchers at the University of Cambridge have discovered that they can stop these cells from invading healthy tissue—not by targeting the cells directly, but by freezing the very environment they move through.

At the heart of this breakthrough is hyaluronic acid, or HA, a long sugar-like polymer that acts as a structural support in the brain. “If you can stop hyaluronic acid from being flexible, you can stop cancer cells from spreading,” said Melinda Duer, a chemist at Cambridge and lead author of the study published in Royal Society Open Science.

Changing the Environment

In many types of cancer treatment, doctors try to poison or remove the cancer cells. Duer and her colleagues went for a different approach. They modified the extracellular matrix—the gooey framework that holds brain tissue together.

This matrix is rich in hyaluronic acid, and under normal conditions, its flexibility allows it to twist into shapes that activate receptors on cancer cells, particularly CD44, a surface protein that tells the cells it’s time to move.

Using nuclear magnetic resonance (NMR) spectroscopy, the researchers showed that at lower concentrations, HA becomes more flexible. That flexibility allows it to fit perfectly into the CD44 receptor, triggering signals that promote cancer invasion.

But when HA molecules were chemically locked in place (cross-linked so they couldn’t move), the cancer cells simply… stopped. “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 neighboring tissue,” Duer said.

The approach works because the cancer cells rely on a very specific kind of molecular handshake. Flexible HA wraps into a conformation that fits snugly into CD44 like a key in a lock. Without that motion, the lock stays closed.

The Mechanics of Invasion

The team tested their theory by growing glioblastoma cells inside gels of varying HA concentrations. In low-concentration gels, where HA was more flexible, cells quickly broke out, extending long, branching arms called invadopodia. Yet in stiffer, higher-concentration gels, the cells stayed put. They didn’t die, but they didn’t move either.

“The cells in high-concentration HA were basically dormant,” said Duer. “It’s as if they were waiting for something to change.”

This discovery helps explain a long-standing puzzle in glioblastoma treatment: why tumors often return at the site of surgery. Surgical trauma frequently causes oedema, or swelling, which dilutes the extracellular matrix. This makes the HA more flexible and potentially reactivates dormant cancer cells.

By contrast, when researchers stiffened HA artificially using a modified version called oxidized HA (oxHA), even dilute gels became hostile to cancer movement. The stiffened matrix mirrored the dormant state, even though its HA concentration was low.

“Our results collectively suggest that the important parameter for HA in cancer progression is its molecular flexibility for binding to CD44, rather than HA molecular weight,” the researchers wrote in the study.

A New Kind of Cancer Therapy?

Rather than relying on toxic drugs that try to infiltrate every tumor cell, this approach works from the outside in, altering the tumor’s environment so the cells can’t get the cues they need to spread.

“Nobody has ever tried to change cancer outcomes by changing the matrix around the tumor,” Duer said. “This is the first example where a matrix-based therapy could be used to reprogram cancer cells.”

While the research is still early and human trials are years away, it opens up a radically new way of thinking about cancer treatment, particularly in glioblastoma, where conventional therapies have largely failed. The five-year survival rate for the disease hovers around 15%.

Crucially, the approach doesn’t depend on penetrating the entire tumor with drugs or radiation. “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,” said Duer.

For now, the team plans to test the technique in animal models to see whether stiffening HA in living brains can prevent recurrence after surgery. They’re also exploring how different tumor types might respond to similar manipulation of their extracellular matrices.

There are challenges ahead. Delivering HA modifiers to the right location in the brain, avoiding unintended effects, and ensuring long-term safety will all require careful study. Still, the idea that brain cancer might be tamed—not with a sledgehammer, but with a molecular tuning fork—is captivating.

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

For now, the team is preparing for the next phase of research—and hoping this discovery marks the beginning of a new chapter in the long, hard fight against glioblastoma.