Scientists have discovered that pancreatic cancer relies on connections to the nervous system to grow and spread. A team from the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) found that the tumor actively reprograms nerve cells to support its survival.
Their study, published in Nature, suggests that blocking these nerve connections could slow tumor growth and make cancer cells more sensitive to treatment.
How the Nervous System Fuels Pancreatic Cancer
In many types of cancer, scientists have found that interactions with the nervous system can promote tumor growth. This is especially true for pancreatic cancer, which is surrounded by a dense network of nerves.
However, while nerve fibers extend into the tumor, the main bodies of these nerve cells (their nuclei) remain outside the pancreas. Until now, it was unclear exactly how cancer cells and nerve cells communicate.
Using a new research method, the team led by Andreas Trumpp analyzed nerve cells in both healthy pancreatic tissue and pancreatic tumors in mice. They found that in tumors, nerve cells undergo significant changes. The cancer alters the activity of many genes in these nerves, creating a unique “tumor-specific signature” that supports tumor growth.
The Lasting Impact of Cancer-Affected Nerves
Even when the primary tumor was surgically removed, the cancer’s influence on nerve cells remained. When researchers implanted new pancreatic cancer cells into mice that had previously undergone surgery, the tumors grew twice as large as in mice receiving cancer cells for the first time.
This suggests that once the nervous system has been altered by cancer, it continues to create a favorable environment for new tumor growth.
Beyond directly supporting cancer cells, the nerves also affect fibroblasts—cells that make up a large part of the tumor structure. These fibroblasts help suppress the immune system, preventing the body from fighting the cancer effectively.
Cutting Nerve Connections to Slow Tumor Growth
To test whether the nervous system was essential for cancer growth, scientists used two methods to block nerve signals: surgery and neurotoxins. In both cases, when the nerve connections to the pancreas were severed, tumor growth slowed significantly.
They also observed changes in the cancer-supporting fibroblasts—genes that usually promote growth became less active, while genes linked to inflammation became more active.
This suggests that nerves play a key role in keeping the tumor environment immunologically “cold,” meaning the immune system struggles to attack the cancer. By cutting these nerve connections, the researchers were able to activate the immune response within the tumor.
Boosting Immunotherapy with Nerve Blockade
One major challenge in treating pancreatic cancer is that it does not respond well to immune checkpoint inhibitors (ICIs), a type of cancer immunotherapy. These drugs work by helping the immune system recognize and attack cancer cells. However, pancreatic tumors are resistant because immune cells cannot penetrate them.
In the study, researchers found that when they blocked nerve connections in mice, the tumors became much more sensitive to immunotherapy. After using a targeted neurotoxin to cut nerve signals, they treated the mice with the immune checkpoint inhibitor nivolumab.
The tumors shrank to just one-sixth of their original size—something that immunotherapy alone had never achieved in pancreatic cancer.
Combining Nerve Blockade with Chemotherapy
The scientists also tested whether chemotherapy could enhance the effects of nerve disruption. Nab-paclitaxel, a common chemotherapy drug for pancreatic cancer, is known to affect sensory nerves, often causing nerve-related side effects.
The researchers found that repeated treatment with nab-paclitaxel significantly reduced the number of sensory nerves in tumors, contributing to the drug’s effectiveness.
However, some nerve fibers remained active and continued promoting cancer growth. To completely cut off nerve support, the researchers combined nab-paclitaxel with a neurotoxin that blocked sympathetic nerve activity. This dual treatment had a dramatic effect, reducing tumor mass by over 90%.
A New Strategy for Pancreatic Cancer Treatment
These findings suggest that pancreatic cancer cannot thrive without its connection to the nervous system. Blocking nerve signals not only slows tumor growth but also makes cancer cells more vulnerable to chemotherapy and immunotherapy.
Dr. Vera Thiel, one of the study’s lead authors, emphasized the significance of these results. “Completely stopping communication between nerves and the tumor, in combination with chemotherapy or immunotherapy, could be a powerful new strategy for treating pancreatic cancer,” she said.
Dr. Trumpp added that this approach might help shrink tumors enough to make surgery an option for more patients. His team is now working with doctors from Heidelberg University Hospital to test these findings in early clinical trials.
While more research is needed, this study offers a promising new way to fight one of the deadliest forms of cancer. By targeting the nervous system, scientists hope to improve survival rates and make treatment more effective for pancreatic cancer patients.
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The research findings can be found in Nature.
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