The scientists on a mission to revolutionise brain tumour research

In January 2018, Baroness Tessa Jowell bravely stood up in the House of Lords and called for more funding and support for people with brain tumours. “For what would every cancer patient want?” she asked. “To know that the best, the latest science was being used – wherever in the world it was developed, whoever began it.”

She stressed the need for investment and international collaboration, so we’re delighted to announce 3 newly-funded, world-class brain tumour research teams that aren’t afraid to think big.

The odds of surviving a brain tumour have remained dismally low for decades. And our Brain Tumour Awards, which were announced in May 2018, are designed to accelerate progress in understanding brain tumours and finding ways to treat them.

From developing tiny particles that could deliver drugs across the barrier surrounding the brain to going back to basics, the teams’ science impressed our expert panel. And they will now receive £18 million to put their research plans in to action.

We spoke to the team leaders about how they plan to use this much-needed cash injection.

New strides across the brain’s protective barrier

Brain tumours are a complex patchwork of cells that can adapt rapidly to cancer drugs. “It’s very unlikely that a single drug is going to do much,” says Professor Neil Carragher, from the University of Edinburgh, who is fronting one of the teams and will also be supported by The Brain Tumour Charity.

“We really need drug combinations.”

To find these combinations, Carragher’s team – including other laboratories from the University of Edinburgh, University of Oxford and the Koch Institute for Integrative Cancer Research at MIT in the US – will scour a chemical library containing thousands of different potential drugs, testing thousands of different combinations on brain tumour samples collected from patients. They’ll speed this process up by using automated, robotic microscopes.

Carragher is all too aware that people are dying from brain tumours right now. He says they’ll be testing all approved drugs, as well as experimental drugs that have passed initial safety testing in people. This means that if an effective drug combination is found, the team won’t have to jump the initial regulatory hurdles needed to get them into clinical testing, which could help get promising treatments to patients faster.

Nanoparticles crossing the blood brain barrier in mice. (Lam. C, F. et al. 2018)

Outsmarting brain tumours’ survival tactics isn’t the only challenge. They’re also shielded from drugs by a protective filter, called the blood brain barrier, that separates the blood from the fluid that bathes the brain. Until now, it’s been a struggle getting any cancer drug through, let alone many. Luckily, the team has a potential nano-sized solution.

Professor Paula Hammond, head of chemical engineering at the Koch Institute, and also part of the team, has invented nanoparticles that can deliver drug combinations across the blood brain barrier.

Once they’ve placed the drug inside the nanoparticle, says Carragher, they make another layer and fit a different drug in a separate compartment. “You have multiple drugs, mixed together in different parts of the nanoparticle,” he says.

The results from the team’s initial lab tests should point to the best drug combination that can be loaded up into these nanoparticles. The hope is that this approach will help old drugs that previously failed to break through the barrier a fresh chance at reaching and targeting the brain tumour.

Designing new brain tumour drugs specifically for children

Professor Richard Gilbertson, from the Cancer Research UK Cambridge Institute, is starting from the position that we need to completely rethink research into childhood brain tumours.

“We’ve not moved the needle in brain tumours for children in the last 50 years,” he says, explaining that that the solution to children’s brain tumours may lie at the start of a brain cell’s life.

“A lot of children’s brain tumours are developmental diseases. Our studies have shown that the biology of cells in a brain tumour of a five-year-old is very similar to a population of cells which existed when the baby was an embryo in the womb,” Gilbertson explains.

We’ve not moved the needle in brain tumours for children in the last 50 years.

– Professor Richard Gilbertson, Cancer Research UK Cambridge Institute

To understand why and how this happens, Gilbertson’s team is going to build a map that details the activity of normal cells in the brain.

“This tissue that was once present when these kids were in the womb is now in the wrong place at the wrong time. By having a neuroscience approach, which looks at normal development and seeing what persists, you can start to look at a whole series of drug targets which wasn’t available before.”

By understanding what’s normal, Gilbertson hopes to build a clearer picture of how these processes go wrong to form a tumour. And he thinks the answer is right in front of us, it just takes careful and meticulous investigation of basic brain biology.

Drugging the ‘undruggable’

Our third team is also hoping to fill in the blanks around brain biology.

They’re focusing on glioblastoma, the most common and lethal brain tumour that kills more people than any other. It’s the disease Tessa Jowell sadly died from.

According to the project’s lead, Professor Steve Pollard from the University of Edinburgh, these aggressive brain tumours live in a paradox. “A large proportion of the tumour cells within the tumours aren’t really active, they’re sleeping,” he says.

These dormant cells are what makes brain tumours so hard to treat. When sleeping cells are inactive, they don’t respond to radiotherapy or chemo. When the patient stops receiving treatment, these dormant cells wake up, and the disease returns.

“We don’t know what defines these sleeping cells, or how they wake up,” says Pollard.

But if they did then they could design small molecules that could stop the tumour growing again. These therapies could either force the tumour cells to permanently stay asleep, or alternatively, force them out of their slumber so treatment eliminates them.

“We’re asking ourselves: ‘how can we drug the undruggable?’” says Pollard. Research suggests it’s more complicated than cells simply being ‘awake’ or ‘asleep’. Understanding the whole range of cell states could point to common molecules on all brain tumour cells, sleepy or awake, that could be useful targets for drugs.

“We know that these cell states are controlled by molecules that turn genes on and off,” says Pollard. So part of the team will be finding new drugs that could intercept these molecules.

Other team members will try to understand why the immune system doesn’t detect these sleeping cells.

“This could help us keep sleeping cells under control and prevent tumours returning.”

Let the research begin

There’s a lot of hard work ahead, but these scientists certainly bring hope to a disease that has cut short many lives. We don’t yet know what they will discover, but we do know these teams offer “the best, the latest science” and bring us one step closer to Baroness Jowell’s wish: “That we can live well with cancer, not just be dying of it. All of us. For longer.”

Gabi