Touching a nerve: How neuroscience could advance our understanding of cancer

When supporters donate to our work, their combined generosity might lead to a new discovery that inches us closer to, for example, a new class of life-saving treatments. Or it might help fund a clinical trial, where experimental new drugs are tested. Occasionally – as for those who support our researchers in Edinburgh or who collectively gave £100 million to help build our flagship Francis Crick Institute in London – their generosity could even help usher in an entirely new field of cancer research.

Seeing the bigger picture

Researchers including our own have long been studying how to effectively channel the body’s immune system to tackle cancer – with some brilliant results. But so far, less attention has been paid to how cancer interacts with other systems in the body, such as the nervous system. Now, an emerging school of thought is calling for a more holistic view of cancer genesis, evolution and impact, instead of immediately zooming in on a tumour or organ. As our chief clinician, Professor Charlie Swanton, said recently: “It’s time to start focusing on cancer as a systemic condition, rather than just a clump of rapidly dividing cells.” And cancer neuroscience could just be the next part of the equation.

Cancer neuroscience – a whole new world of opportunity

As modern academic fields, neuroscience – the study of the structure and function of the nervous system – and cancer biology have co-existed for over a hundred years. So why does the role of the nervous system in cancer progression remain largely unexplored? Dr Leanne Li, group leader of the Cancer Neuroscience Laboratory at the Crick, suspects it has to do with the high entry barriers in these fields, making it difficult to find experts who straddle both.

Leanne, who is from Taiwan and studied in Switzerland and the US before coming to the Crick, says crossing these academic boundaries is akin to switching between cultures. “Every culture has a unique language and set of customs. It’s the same with cancer biology and neuroscience,” she explains. “Cancer is hectic and unpredictable, with mutation being one of the defining hallmarks. But the nervous system is much more ordered and logical. We know that it regulates whole-body homeostasis in a well-tuned, sophisticated manner.”

Dr Leanne Li

The approaches, techniques and even mentalities required to study the two fields are therefore naturally different. But by embracing these idiosyncrasies, researchers could lead us to surprising new insights. “By looking at the same question from distinct perspectives,” Leanne says, “And trying to answer it by applying rules from different fields, you begin to see a whole new world of opportunity.”

So what do these pioneering researchers hope to find out? Broadly speaking, the field can be cleaved into two key areas of investigation, both of which we’re diving into thanks to ongoing philanthropic support.

Repurposing the wheel

One group of cancer neuroscience researchers is interested in how cancers of the central nervous system – for example, brain tumours – interact with other brain cells to survive and grow. Dr Dirk Sieger, who is studying a common type of brain tumour called glioblastoma, is one of them.

Dirk moved to the University of Edinburgh in 2012, where he was inspired by world-leading neuroscience and brain tumour experts to ask new questions about cancer’s reliance on healthy biological systems. By 2015, he had been granted a Cancer Research UK Career Establishment Award, allowing him to set up his first research group into this very area.

“Tumours don’t reinvent the wheel,” Dirk concludes. “They repurpose neural mechanisms and signals that are already in place for other healthy biological processes.” One of these mechanisms involves brain-specific immune cells called microglia. These industrious cells are involved in brain development and receive and respond to signals from other parts of the brain. Microglia also possess classic immune cell functions and swoop in to repair damage, clear cellular debris and target harmful cells.

Dirk’s initial findings supported the theory that glioblastoma tumours repurpose certain neural

Dr Dirk Sieger

mechanisms to mimic signals from a healthy brain. This misleads the microglia, setting them off on ill-fated tasks to support the tumour, rather than mounting an anti-tumour response. His team is now building on this knowledge with new Cancer Research UK funding to test their theory that microglia don’t just help tumours with more menial tasks, but also assist them in forming networks with other cells. “Microglia have long, fine protrusions, which they send out to probe the environment and contact neighbouring cells,” he explains. “We have some evidence that this contact makes the tumour more aggressive, invasive and resistant to therapy.”

Dirk hopes that by learning more about this process, his team can find a way to return the microglia to their original functions – thus cutting off this vital lifeline for the tumour.

Speaking the same language

But what about cancers in other parts of the body? How do cancers outside the central nervous system, such as lung cancer, interact with nerve cells to survive and grow?

Leanne has just set up her multi-disciplinary group at the Crick, but based on her preliminary findings, she too has concluded that other cancer cells can hijack signals used by nerve cells for their own benefit.

Being two distinct cell types with seemingly minimal similarity, you might expect that nerve cells and cancer cells would “speak different languages”. But Leanne found that some cancer cells adopt the nerve cells’ language. Whereas Dirk is looking exclusively at microglia – found only in the brain – Leanne found that this was the case with nerve cells that are responsible for functions around the body. This led to her current hypothesis: that the body can “communicate” with a tumour through the nervous system.

“There are different forces being applied,” says Leanne. “There are nerve signals that are trying to control the tumour, and others, overtaken by the tumour, that promote its growth. If we can identify how these opposing forces work, we could tip the balance in favour of tumour regression.”

Leanne’s approach is unique because, while a handful of teams globally are studying tumours outside the central nervous system, they’re homing in on specific cancer types and pathways. Instead, she says, “I want to take a systematic approach to identify general rules across different types of cancers, and not just primary tumours but also metastasised ones.” Finding such a rule would be a major turning point for how we understand cancer evolution.

Spirit of collaboration

Both Leanne and Dirk credit their respective institutes with creating the perfect conditions for testing their bold hypotheses. At the Crick, Leanne need only travel upstairs to brainstorm with an expert in neuroscience. And that spirit of collaboration is shared at Edinburgh. “Everybody’s always open to teaming up to explore new ideas,” Dirk emphasises. “You get valuable input from many different perspectives.”

Crucially, thanks to our supporters, we can offer them long-term support – both groups will receive funding for at least six years. “It gives us the opportunity to spend time on unexpected findings and dig deeper,” says Dirk. “Often, that will take you to novel findings that can make all the difference.”

Their projects may be in the early stages, but Leanne and Dirk believe they could lead to new treatments, and that other pre-existing treatments could also be redeployed for people with cancer. For example, Leanne believes that current treatments for various neurological diseases like Parkinson’s could be repurposed in the future to redirect the misfiring nerve cells that help cancer grow.

As James Reynolds, a long-time Cancer Research UK supporter and one of the Crick’s founding philanthropists, once told us: “On my first visit to the Crick, when it was still a construction site, my wife and I walked through the labs and said to each other, ‘cancer will be defeated in this building.’” With bold new approaches like cancer neuroscience, we’re getting closer to the day when his hopes for the institute – and humankind – are realised.