Modulating Neural Signaling in the Treatment of Pancreatic Cancer
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant diseases, with an overall survival (OS) rate of 9%. The resistance of PDAC to treatment has been attributed in part to the tumor microenvironment and the complex desmoplastic stroma, which comprises numerous cells including nerves. Although the least well-studied, recent evidence has suggested a role for nerves in the development of cancer. All solid tumors, apart from CNS tumors, are innervated by axonal fibers arising from the peripheral nervous system (PNS). In most solid tumors, there is a marked increase in neural density and nerve size during cancer growth. Experimental model systems have shown a direct contribution of nerves to the development of prostate cancer, basal cell carcinoma, breast cancer, and from our group, of gastric cancer. We recently reported for the first time that parasympathetic signaling can profoundly suppress pancreatic cancer growth, and this inhibitory effect of muscarinic signaling has now been confirmed in models of breast cancer. The effect of nerves on tumor growth may be direct or indirect. Nerves modulate growth directly through interactions with cancer cells or indirectly through interaction with the tumor microenvironment (TME). In early development and during regeneration, nerves promote the growth of stromal cells derived from the mesenchymal blastema. The purpose of this research is to investigate both the direct and indirect effects of muscarinic cholinergic signaling in suppressing PDAC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2022
- Accession Number
- AD1192066
Entities
People
- Susan Bates
- Timothy C Wang
Organizations
- Columbia University