A continuous approach of modeling tumorigenesis and axons regulation for the pancreatic cancer.

The pancreatic innervation undergoes dynamic remodeling during the development of pancreatic ductal adenocarcinoma (PDAC). Denervation experiments have shown that different types of axons can exert either pro- or anti-tumor effects, but conflicting results exist in the literature, leaving the overall influence of the nervous system on PDAC incompletely understood. To address this gap, we propose a continuous mathematical model of nerve-tumor interactions that allows in silico simulation of denervation at different phases of tumor development. This model takes into account the pro- or anti-tumor properties of different types of axons (sympathetic or sensory) and their distinct remodeling dynamics during PDAC development. We observe a "shift effect" where an initial pro-tumor effect of sympathetic axon denervation is later outweighed by the anti-tumor effect of sensory axon denervation, leading to a transition from an overall protective to a deleterious role of the nervous system on PDAC tumorigenesis. Our model also highlights the importance of the impact of sympathetic axon remodeling dynamics on tumor progression. These findings may guide strategies targeting the nervous system to improve PDAC treatment.

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Copyright © 2024. Published by Elsevier Ltd.

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Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.