Pancreatic cancer remains one of the most challenging cancers to detect early and treat effectively. Standard therapies often fall short, prompting researchers to explore novel approaches to disrupt disease progression. Recent findings suggest a critical, previously underappreciated role for the nervous system in the development of pancreatic cancer, offering a potential new therapeutic target.
A study published in , detailed in reports, reveals that interactions between nerves and cancer cells begin much earlier than previously understood. The research indicates the nervous system actively participates in pancreatic cancer development even before a tumor is fully formed.
Researchers at the Cold Spring Harbor Laboratory (CSHL) discovered that a type of tumor-supporting cell, known as myCAFs, releases signals that attract nearby nerve fibers. Once these nerve fibers arrive, they interact with the myCAFs, creating a favorable environment for cancer to progress. This interaction establishes a feedback loop that fuels the disease.
Further experiments, utilizing both mouse models and human cells, illuminated a strong reciprocal relationship between myCAFs and the nervous system. The myCAFs release chemical signals that draw nerve fibers from the sympathetic nervous system – the part of the nervous system responsible for the “fight or flight” response. These nerve fibers, in turn, release norepinephrine, a neurotransmitter that binds to the fibroblasts and triggers a surge in intracellular calcium. This calcium spike further activates the myCAFs, promoting the growth of precancerous lesions and attracting more nerve fibers, thereby reinforcing the cycle and driving disease progression.
Significantly, when researchers used neurotoxins to suppress the sympathetic nervous system in mice, they observed a reduction in fibroblast activation and a nearly 50% decrease in tumor growth. This finding, reported by SciTechDaily, suggests that disrupting this nerve-cancer alliance could be a viable therapeutic strategy.
Because this interaction occurs so early in the disease process, researchers believe targeting it could open the door to new treatment options. The study suggests that existing medications, such as doxazosin, could be effective when used in combination with established therapies like chemotherapy or immunotherapy.
Scientists at the German Cancer Research Center (DKFZ) and the Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) have also been investigating the connection between pancreatic cancer and the nervous system. Published in , their research, detailed here, demonstrates that the tumor actively “reprograms” neurons for its own benefit. Using advanced light-sheet fluorescence microscopy, researchers visualized the dense network of neuronal structures that innervate pancreatic tumors in mice. Blocking nerve function in these models inhibited cancer growth and increased the sensitivity of tumor cells to both chemotherapy, and immunotherapy.
This isn’t an isolated finding. For several years, scientists have observed interactions with the nervous system in various types of cancer, often promoting tumor growth and survival. This interplay is particularly pronounced in pancreatic cancer, which is heavily interwoven with a dense network of nerves.
Beyond targeting the nerve-cancer interaction, researchers are also exploring other avenues for improving pancreatic cancer treatment. A team at the University of California, Riverside (UCR) has developed a “molecular crowbar” strategy to degrade the oncogenic enzyme Pin1, which is overexpressed in many tumors, including pancreatic cancer. This approach not only targets cancer cells directly but also addresses tumor-supporting cells like cancer-associated fibroblasts and macrophages, potentially overcoming treatment resistance. The UCR team is collaborating with scientists at City of Hope to further test these degraders in pancreatic and gastrointestinal cancers, aiming to develop a new class of therapeutics that “remove” harmful proteins rather than simply blocking them.
Ongoing research, as highlighted in a contemporary review published in , emphasizes the complexity of pancreatic cancer management and the need for multidisciplinary care. Multimodality therapy, combining surgical resection, chemotherapy, and potentially these emerging nerve-targeted approaches, will likely be crucial for improving outcomes.
Researchers are now focused on identifying methods to disrupt the interaction between fibroblasts and nerves. While these findings are promising, further investigation is needed to determine the optimal strategies for translating these discoveries into effective treatments for patients with pancreatic cancer.
