The relationship between cancer and the nervous system has been a curiosity and mystery for nearly two centuries. Jean Cruveilhier’s initial observations in the early 19th century highlighted tumors growing along nerves, a phenomenon that puzzled scientists for generations. Fast-forward to the 21st century, and groundbreaking research is revealing the critical role nerves play in cancer progression.
The Birth of Cancer Neuroscience
In 2013, research led by Paul Frenette showed that autonomic nerve fibers played a role in regulating the growth of prostate tumors in mice. Similarly, researchers led by Timothy Wang demonstrated that severing the vagus nerve’s connection to the stomach halted cancer growth in mice, underscoring the relationship between nerves and cancer cells.
These findings marked the emergence of cancer neuroscience, a field dedicated to exploring how the nervous system influences cancer progression. In 2019, two groups of researchers independently found that tumor cells in the brain created synapses with nearby neurons, integrating into neural circuits and fueling tumor progression through electrical activity. Subsequent research has shown that synapses also form between neurons and cancer cells in other parts of the body.
Seeking Refuge: The Safe Harbor Hypothesis
Jami Saloman and colleagues proposed the safe harbor hypothesis to explain why tumors seek protection from nerves. This theory suggests that tumors exploit the fact that nerves regulate the immune system’s response to pathogens, providing a sanctuary for tumor cells from immune attacks. “It’s really like the tumor cells hijack this evolutionary protection and turn it into something bad,” said Saloman. “Tumor cells might be more protected from an immune response if they’re near these nerves that are shutting down the immune system. It would be like a hideout place where they could keep away from the immune response, or at least, a less severe immune response.” Two ongoing clinical trials are evaluating meclofenamic acid, an anti-inflammatory, and perampanel, an anti-seizure medication, to treat brain cancer by severing the connections between tumor cells and neurons.
Tumors as Faux Organs
Beyond protection from the immune systems, tumors also need nearby nerves to innervate them as if they were new organs. Research by Paola Vermeer demonstrated that tumors use signaling molecules to attract sensory nerves, facilitating tumor growth. Blocking these signals emerged as a promising strategy to restrict this growth.
Implications for Cancer Detection and Treatment
The brain’s ability to detect cancer-related changes in the body opens exciting possibilities for early cancer detection and monitoring. Research by Jeremy Borniger aims to use machine learning algorithms to recognize cancer signatures in brain waves, potentially leading to noninvasive diagnostic tests.
A deeper understanding of neuro-cancer connections may also uncover new ways to treat cancer and enhance the effectiveness of existing therapies. For instance, a Phase II clinical trial evaluated the effects of giving patients a beta blocker one week before breast cancer surgery. This treatment reduced the activity of the sympathetic nervous system, which is often heightened by surgical stress. The results showed that this pretreatment led to a decrease in gene expression and immune cell markers commonly linked to cancer recurrence, indicating a potential new strategy to improve cancer treatment outcomes.
Moving Forward
As the study of cancer neuroscience evolves, researchers will continue to investigate ways to leverage the connections between cancer and the nervous system to develop more effective and targeted treatments. “We’re in a similar space as cancer immunotherapy was in the late ‘80s when it was clear that it was important, but it wasn’t clear exactly how it worked and how we could take advantage of it. But I think for the next 10 years that it’ll be the same story for cancer neuroscience,” said Borniger.
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