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Researchers from the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) have made a groundbreaking discovery in the fight against pancreatic cancer. Their study, recently published in Nature, reveals that pancreatic tumors actively reprogram neurons to support their growth.
The Role of the Nervous System in Pancreatic Cancer
Scientists have long observed interactions between cancer and the nervous system in various tumor types. However, pancreatic cancer appears to be uniquely intertwined with nerve cells. The study shows that the disease reprograms the genetic activity of neurons, creating an environment that facilitates tumor expansion.
Even after the surgical removal of the primary tumor, the nervous system retains its cancer-supportive properties. When researchers reintroduced pancreatic cancer cells into mice that had previously undergone surgery, the new tumors grew at twice the rate compared to tumors in mice without prior exposure.
Blocking Nerve Function to Slow Tumor Growth
The research team tested the impact of severing nerve connections to the pancreas using surgical techniques and specialized neurotoxins. This intervention significantly slowed tumor progression, decreased cancer cell proliferation, and enhanced the effectiveness of immunotherapy.
Lead researcher Vera Thiel explained, “Neuronal connections in pancreatic cancer appear to suppress immune activity, allowing tumors to evade detection. By disrupting these connections, we can stimulate the immune system and make tumors more susceptible to treatment.”
Enhanced Immunotherapy Effectiveness
One of the key findings was that blocking neural input transformed pancreatic tumors from “immunologically cold” (resistant to immunotherapy) to “immunologically hot” (responsive to treatment). In experiments, severing nerve connections made tumors more sensitive to the checkpoint inhibitor nivolumab, reducing tumor mass to one-sixth of its previous size.
Combining Nerve Blockade with Chemotherapy
The researchers also explored the combined effect of nerve disruption and chemotherapy. Nab-paclitaxel, a standard chemotherapy drug for pancreatic cancer, was found to weaken sensory nerve fibers. When combined with neurotoxin-based nerve blockade, the treatment produced a synergistic effect, reducing tumor mass by more than 90%.
Andreas Trumpp, a lead researcher, noted, “Completely blocking the communication between nerves and tumors in combination with chemotherapy and immunotherapy could be a transformative strategy for treating pancreatic cancer.” Early clinical trials are now being planned in collaboration with Heidelberg University Hospital.
The Importance of Animal Research
The study was conducted using mouse models to understand the complex interaction between nerves, cancer cells, and the immune system. These biological systems cannot be fully replicated in cell cultures, making animal research essential for such discoveries.
Looking Ahead
This research paves the way for potential new treatments that target the nervous system to combat pancreatic cancer. If successful in clinical trials, this approach could significantly improve patient outcomes, potentially making previously inoperable tumors treatable.
Disclaimer
This article is based on preclinical research. While the findings are promising, further clinical trials are necessary to determine their applicability to human patients. Readers should consult healthcare professionals for medical advice and treatment options.
