# Peripheral Nerves in Cancer: Regulatory Roles and Therapeutic Strategies

## TL;DR

This paper explores how cancer cells interact with peripheral nerves, forming networks that promote tumor growth and metastasis, suggesting new therapeutic strategies targeting these interactions.

## Contribution

The paper provides a comprehensive review of how cancer cells hijack and remodel the nervous system to advance tumor progression.

## Key findings

- Cancer cells induce new neural axon growth and form neural fiber networks within tumors.
- Nerve-derived molecules promote perineural invasion and regulate tumor malignancy traits like metastasis and therapy resistance.

## Abstract

Cancer neuroscience has emerged as a transformative frontier in oncology research, focusing on the interplay between cancer cells and the nervous system. Cancer cells establish tumorspecific neural networks within tumor tissues via neurotrophic hijacking. The nervous system regulates tumor initiation, progression, and metastasis either directly by regulating signal transduction in tumor cells or indirectly by modulating the tumor microenvironment (TME). The positive feedback loop between cancer cells and nerves promotes tumor progression. Deciphering the regulatory role of nerves in tumor progression may yield novel anticancer therapeutic options. In this review, the interaction between nerves and cancer cells is described, including how cancer cells hijack and remodel nervous system structure and function, and how neuron‐signaling regulates cancer cell growth directly or indirectly through modulating the TME. This evidence of the critical role of nerves in the malignant phenotype of tumors indicates the potential of using neuron‐signaling targeting strategies in cancer treatment. By summarizing these findings, this review aims to provide comprehensive insights into the interaction between nerves and cancer cells, paving the way for neuron‐signaling‐based anticancer therapies.

The interaction between cancer cells and peripheral nerves: (1) tumor cells could induce the growth of new neural axons and constructing a neural fiber network within the tumor tissue through secreting nerve growth factors; (2) nerve‐derived bioactive molecules can induce perineural invasion of tumor and regulate the malignant phenotype of tumor, such as immune invasion, proliferation, metastasis, angiogenesis, and therapy resistance (created with BioRender.com).