A growing body of research suggests tumours rely on proteins and genes that are unique to the nervous system to persist in the body.
The neural network in a healthy pancreas (left) and in a pancreatic tumour (right).Credit: Ref. 4
When Jami Saloman gave capsaicin, the molecule that gives peppers their signature spice, to newborn mice in 2015, she expected that it would ease the pain of the pancreatic tumours that the mice were bred to develop.
The mice had a mutation that is present in 90% of people with pancreatic adenocarcinoma (PDAC), the most lethal form of the cancer. Typically, these mice develop precancerous lesions by eight weeks of age and survive little more than a year. Saloman, who at the time was a postdoctoral researcher studying pain, knew that high doses of capsaicin blocked sensory nerve signals, and, therefore, might block the pain of the cancer in mice.
Nature Outlook: Pancreatic cancer
Surprisingly, it seemed to do much more than that. None of the mice given capsaicin developed pancreatic cancer, even after nearly 19 months1. “We were really shocked,” says Saloman, who is now a neurobiologist at the University of Pittsburgh in Pennsylvania. And “it completely changed the trajectory of my career”, she says.
Saloman had stumbled into the field of cancer neuroscience, in which researchers were just beginning to investigate the relationship between cancer and the nervous system. Instead of studying pain, she opened a lab investigating what sensory nerves do in the spaces in which cancers grow, known as the tumour microenvironment.
A decade later, she and other researchers have gained some understanding of how cancers use the body’s nervous system to survive, grow and spread. Pancreatic cancer is particularly good at it: cancer cells spread into the nervous system in nearly everyone with the disease. In colon cancer, by comparison, around 30% of people show signs of such neural invasion. Pancreatic cancer cells also overexpress genes with neuronal functions, influence communication between nerves and the immune system, and take amino acids from neurons. Without the nervous system, it seems, pancreatic cancer would be an entirely different, and probably less deadly, disease.
Currently, only around 13% of people with pancreatic cancer survive for five years after diagnosis, says Elizabeth Jaffee, co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care at Johns Hopkins University in Baltimore, Maryland. But a growing understanding of the tumour microenvironment and the involvement of neurons could provide an opportunity to improve that, she says. “This is going to lead to new therapies.”
Cancer-nerve connections
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