Tumor innervation in non-central nervous system tumors: origins, mechanisms, and phenotypic plasticity.

Authors

Yonghui Zhang, Zhixin Ye, Ying Wang, Siying Tang, Gang Chen

Published in

Trends in neurosciences. Oct 20, 2026. Epub Oct 20, 2026.

Abstract

The peripheral nervous system has emerged as an important regulator of solid tumor biology. We synthesize recent advances in cancer neuroscience, focusing on three interconnected themes: the cellular origins of tumor-associated nerves, the molecular mechanisms that govern neural recruitment and remodeling, and the resulting phenotypic plasticity within the tumor microenvironment. Tumor innervation arises through axon extension from pre-existing nerves, recruitment of neural precursors, and neuron-like transdifferentiation of non-neuronal cells. These processes are driven by neurotrophic factors, axon guidance cues, extracellular vesicles, and stress-associated pathways. The functional consequences of innervation are context-dependent, with sympathetic, parasympathetic, and sensory inputs exerting distinct effects across tumor types and stages. We conclude by outlining key challenges and future directions for therapeutic translation.

PMID:
42901812
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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