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The video I am watching feels like a scene from a horror movie. At the centre of the screen is a blood-red mass – in reality, a massively magnified pancreatic tumour, vividly dyed as if to highlight its malevolence. It crawls around, luring in a purple tendril, which is actually the long, spindly arm of a living nerve cell. When the mutant growth has this in its grasp, it slowly rolls along the filament towards the neuron’s bulbous body. Once there, things will become even more sinister. The cancer will take shelter, steal nutrients from the neuron and replicate itself. “It’s very creepy,” says .��

Hwang, whose team at Harvard University recorded this footage, has recently joined a growing number of scientists in the new field of cancer neuroscience. They are mapping out interactions between tumour cells and the nerve cells surrounding them – and shattering the long-held belief that these are of little significance. In fact, their findings reveal that nerves play a central role in cancer: they help tumours grow, increase their ability to spread around the body and even undermine the immune system’s efforts to fight the disease.��

While some of the ways that tumours manipulate nerves are truly chilling, a growing understanding of this cellular dialogue is inspiring new cancer therapies. This field is so hot right now that two researchers have just been awarded the world’s largest prize for neuroscience research. “There has been an explosion of interest in cancer neuroscience in the past decade,” says at Monash University in Melbourne. “I think this will be the next big thing in cancer treatments.”��

Cancer researchers first found nerve cells in tumours , but this insight was shelved for more than a century. Then, pathologist , now at the University of Texas Health Science Center at Houston, decided to take a closer look. While waiting for his medical licence in 1998, he became curious about a mysterious phenomenon he had seen time and again called perineural invasion. It describes how the most aggressive cancer cells tend to wrap around and migrate along nerves – just like in the video Hwang showed me. At the time, clinicians had already linked this to poorer survival outcomes. “But nobody knew how it happened,” says Ayala. In search of answers, he mixed human cancer cells and mouse neurons in a lab dish. What he saw astounded him. The cells grew towards each other, establishing a mutual connection that . “It was a eureka moment for me,” he says.����

Unfortunately, most other cancer researchers didn’t see it that way, too busy focusing on unpicking the genes that drive cancer to pay much attention to nerves. Undeterred, Ayala continued his work and, in 2008, he and his colleagues showed that tissue samples taken from the prostates of men with prostate cancer contained .������

Another milestone came in 2013, thanks to the findings by at the French National Institute of Health and Medical Research in Paris and her colleagues. They had injected human prostate cancer cells into mice and found they could by slicing out nerves around the prostate or destroying them with a chemical.����

“That was an eye-popping experiment,” says at Roswell Park Comprehensive Cancer Center in New York state. “It really showed that tumours require nerves to survive, just like they need blood vessels or oxygen.”��

A year later,�� at Columbia University in New York City and his colleagues managed to slow tumour growth in mice by from reaching stomach tumours – either by using Botox or by cutting the nerves. In combination with chemotherapy, this increased the animals’ chances of surviving for more than a month by more than 20 per cent compared with mice that had only chemotherapy. ��

Nerves that feed tumours

“Since then, the field has really grown remarkably,” says Wang. A slew of mouse studies showed that many types of tumours, including breast, skin and pancreatic, into their lair and then feed on proteins called growth factors that the neurons produce. This sets up a vicious cycle, where larger tumours recruit even more nerves and grow even bigger on their growth factors. “We now think of cancer more like an organ,” says Wang. “Every organ or limb requires nerve outgrowth to develop – so the idea that nerves are the master controller of cancer growth makes a lot of sense.” ��

However, unlike organs, tumours don’t always stay in one place; cancer cells often spread to distant sites, making treatment especially difficult. And it turns out that nerves can encourage this migration, too. When Sloan and her team used a drug to amplify signals in nerves in mice, they found that this of breast cancer to the lungs. The neural signals appear to increase the growth of tubes called lymphatic vessels that drain fluid from tumours. This, in turn, provides the cancer with additional routes through which to migrate. “You get many more pathways for cancerous cells to escape,” says Sloan. Dampening these signals with beta blockers – common drugs that are used to treat heart failure, anxiety and migraines – had the opposite effect.����

It gets worse, though. The same neural signals also seem to suppress the body’s own defences against cancer. Repasky and her colleagues have found that they push cancer-fighting immune cells called T-cells , making them less able to destroy tumours. “When the immune cells get to the tumour, nerves are there – and one function of those nerves is to suppress the immune system,” says Repasky. And in a “double whammy”, she says, the same nerves also that supports tumour growth.����

A mountain of evidence in mice now points to neurons as allies of cancer – but the crucial question is whether the same things are happening in people. To explore this, researchers have taken several approaches, including analysing tumour samples and finding that people whose growths contain more nerves from the disease. They have also found that spinal cord injuries seem to reduce the risk of some cancers, presumably by disrupting nerve signals to tumours. In a meta-analysis involving more than 35,000 men with spinal cord injury and more than 158,000 men without, the former had about as the latter. ��

Yet more evidence comes from people taking beta blockers. For example, in 2021, Sloan’s team sifted through the health records of more than 4000 women with heart conditions who also had breast cancer. At the time of their cancer diagnosis, 136 were already taking the beta blocker carvedilol. More than five years later, these women were about as those who hadn’t taken beta blockers. Admittedly, other factors may have influenced the results, such as people’s dietary or exercise habits. Nevertheless, Sloan thinks there is a real signal: “If you look at the now hundreds of beta blocker studies across lots of different cancer types, on the whole, they show a protective association or they don’t find any link, and not too many show an adverse one.”

Recent research even suggests why these results are variable: different tumour types respond distinctly to various branches of the nervous system. For instance, so-called sympathetic nerves, which coordinate the fight-or-flight response, are key drivers of growth in . On the other hand, parasympathetic nerves, which underpin the body’s rest-and-digest response, seem to slow the growth of breast and pancreatic cancer. “They’ve got this yin and yang,” says Wang.����

But the picture is far from simple: parasympathetic nerves can promote the growth of stomach, prostate, head and neck cancers. Moreover, in a new study, Wang found that sensory nerves, which detect things like pain, temperature and the state of internal organs, . And it gets weirder: tumours can also make nerve cells switch from one type to another. In 2020, researchers showed that tongue cancer cells shuttle short genetic codes into sensory neurons, causing them to behave , which more strongly support the tumour’s growth.��

In a further twist, some cancer cells can acquire neuron-like properties, allowing them to directly tap into the nervous system’s electrical activity. This discovery was made independently in two of brain cancers published in 2019. It is this work that won the 2025 Brain Prize, which is worth €1.3 million, for at the German Cancer Research Center in Heidelberg and at Stanford University in California. Winkler and his group collected samples of one of the most lethal cancers – glioblastoma – and mixed these with healthy neurons in a lab dish. Then they electrically stimulated the neurons, causing them to release potassium ions, which nerve cells do when generating an electric current. The surprise, however, was that this sparked , which then amplified the electric signals among them.����

Lethal electrical activity

Since then, evidence has emerged suggesting brain tumours that are . Research found that people whose tumours were highly synced with the electrical activity of healthy regions of their brains survived an average of 71 weeks after diagnosis, whereas those with less electrically active tumours survived for an average of 123 weeks. “The brain cancer is modulating electrical networks in a way that’s determining patient outcome,” says Winkler.��

That’s not all. In their 2019 studies, Winkler and Monje also discovered that some brain cancer cells can form junctions called synapses with healthy neurons. Until then, synapses had been thought to be exclusively a feature of neurons and some of the cells that help them to function, allowing them to transmit messages from one to another by releasing chemicals. So, the researchers were shocked to observe tumour cells developing these structures and using them to fuel their growth. “We found something crazy,” says Winkler. When Monje’s team used an epilepsy drug called perampanel to block signals sent across the synapses that had formed between cancer cells and neurons, this halved tumours’ growth rates. ��

Winkler and his team have since found that – in mice at least – synapses can also form between healthy neurons and skin and breast cancer cells that have spread to the brain. In a study that has yet to be peer-reviewed, they showed that disrupting these synapses with perampanel . And just this year, Wang’s team found synapses between . Again, these fuelled tumour growth.����

Amid this flurry of insights, researchers have begun to set their sights on the clinic. “What I’m most interested in is making a difference to patients,” says Sloan. In 2020, she and her colleagues randomly assigned 60 women who were newly diagnosed with breast cancer to take either a daily dose of the beta blocker propranolol or placebo pills. Analysing tumour samples excised from the women a week later, the team found the cancer cells to be substantially , in those who had taken propranolol. Tumours from this group also contained more immune cells that help to destroy cancer. “That’s only from seven days of treating them with a beta blocker to block neural signalling – so just imagine how longer-term treatment with these drugs could potentially affect the cancer,” says Sloan.��

Repasky has also seen promising results from an initial trial that tested in nine people with skin cancer. The tumours’ responsiveness to the combination therapy was almost twice what the researchers had anticipated based on previous immunotherapy-only studies, “meaning more of their tumours either shrank or disappeared than we anticipated,” she says. The researchers are currently conducting a larger phase II trial, with results due later this year. Repasky is also trialling the approach against breast cancer, oesophageal cancer and multiple myeloma, which develops from plasma cells in bones.��

Meanwhile, Winkler is testing epilepsy and arthritis drugs that either interfere with cancer-neuron synapses or electrical signals in cancer cells to find out whether they can benefit people with glioblastoma. (Intriguingly, his team has just reported that the drug nab-paclitaxel, which is a standard chemotherapy treatment for breast and pancreatic cancers, may work in part by .)��

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Many of the drugs being trialled are “very inexpensive, widely available, and well tolerated”, so they have a real chance of success, says Sloan. But there is one major roadblock: pharmaceutical companies are reluctant to fund trials that repurpose drugs with expired patents. “There’s no money to be made,” says Sloan. To get around this, Winkler and his team are designing novel drugs to treat brain cancers using insights gained from research in mice on drugs that seem to have the potential to tackle a variety of cancers. However, Repasky argues there is another way to entice Big Pharma companies: potentially finding that their newer drugs are more effective when taken in conjunction with existing ones. “That would be a marketable idea”, she says.

It is an exciting time for cancer neuroscience. And my meeting with Hwang left me with another intriguing thought. If the pain some people experience with cancer is linked to nerves within their tumours, perhaps drugs that target these nerves can also act as painkillers. Hwang’s team is currently exploring this: “The idea is that at the same time we’re treating your cancer, you’re also feeling much better,” he says.

“You can’t say that for a lot of treatments being developed.”��