On the threshold of an emerging field that brings together neuroscientists and cancer biologists, Leanne Li is leading a Cancer Grand Challenges team investigating the hidden circuits that connect tumours and the nervous system. Adjusting the signals they send could be a new way to treat cancer.
Small cell lung cancer cells (magenta) closely interacting with nerve fibers (yellow). Credit: Cancer-Neuroscience Laboratory at the Crick, Nature.
Most of us never give a thought to interoception, yet we rely on it constantly. It’s the brain’s ability to monitor our internal world: the flutter of hunger, the shifting of hormones, the subtle discomfort that tells us something is off. Seen as the system that keeps the body in balance, interoception is now at the centre of a bold scientific question: could the brain also be monitoring cancer?
“I think about this every day and night – it’s even in my dreams,” says Leanne Li, who leads the Cancer-Neuroscience Laboratory at the Crick. “I want to know how the nervous system is tracking and influencing the entire course of tumour formation and progression.”
“Although scientists have known that nerves are present inside tumours for more than a century, it’s only recently that we have started to appreciate the powerful control of the nervous system over tumour growth and the exciting potential to harness the nervous system to treat cancer,” she adds. “But the picture appears to be much more complex. There’s been some significant advances in our understanding of interoception in the past few years, thanks to groundbreaking discoveries from our own team members, so it felt like the right moment to bring these fields together.”
Leanne, a cancer biologist, has assembled a multidisciplinary team of neuroscientists, neuroimmunologists and neuroprosthetic experts across the US, Switzerland, Portugal and the UK – many of whom have never worked on cancer before.
Their goal is deceptively simple, to understand the conversation between the nervous system and tumours – and learn how to intervene.
The team will start by charting how tumours in the lung, pancreas and colon connect to the nervous system. Using advanced imaging, techniques that trace where neurons project to and powerful technology that details each cell’s gene activity, they will track the two-way flow of signals between tumours and the brain. As Leanne explains, “This tumour-brain map will help us to identify which circuits help the cancer grow and which ones hinder it.”
Early evidence suggests these neural circuits differ depending on where a tumour appears and which genes are driving it. That could explain why cancers of the same type sometimes behave very differently.
Cancers don’t just affect the organ where they’re located; they can wreak havoc across the body, causing symptoms such as fatigue, appetite loss and weight changes. Leanne’s team, coined ‘InteroCANCEption’, wants to understand the neural pathways that influence these effects, and how infections or inflammation might reshape them in ways that accelerate cancer growth.
For Leanne, these ideas tie back to her clinical training in Taiwan. She recalls how some patients would return year after year with vague, persistent symptoms long before scans revealed a tumour. “The nervous system constantly surveys the internal environment and, crucially, is involved in changes like chronic inflammation, which is linked to cancer development. I kept wondering whether the brain was detecting the earliest stages of tumour formation, before we could see anything in the clinic. And if the tumours are already formed and the patients are very ill, could we harness the nervous system to fight the cancer.”
Current cancer treatments are heavily focused on targeting the tumour or the immune system, either forcing cancer cells to die or recruiting the immune system to attack them. Leanne sees another treatment possibility where neuromodulation – a technology where signals to or from the nervous system are altered – could come into play.
With the team’s neuroimmunology expertise, they’re exploring how neural signals influence the immune system’s response to cancer and whether altering these signals would boost patients’ responses to immunotherapy.
“If we can alter the way the nervous system communicates with tumours, it could be a powerful way to treat cancer,” she says. “Instead of attacking the tumour head-on, we could use neuromodulatory treatments to gently adjust the circuitry that regulates its growth or how the body responds to it. This could be an effective and targeted way to treat cancer.”
In particular, the team is taking advantage of advances in the neuroscience field, including small molecules and neuroprosthetics that are initially developed for patients with neurological diseases. They see enormous potential to repurpose these treatments for cancer patients.
The InteroCANCEption team is working at the frontier of a field that barely existed a decade ago. Bringing together two disciplines as complex as cancer biology and neuroscience is no small undertaking. But Leanne is clear about the challenge. “People sometimes call this 'high-risk’ research, but I don’t think that’s the right word,” she says. “We have ambitious aims, but we’re approaching them rationally, hoping that taking the path less travelled might lead to a completely new and more effective way of treating cancer.”
