The nervous system is now recognized as a pivotal regulator of cancer, marking a paradigm shift that recasts nerves from passive bystanders to active drivers within the tumor microenvironment (TME). This review defines the "neural niche," differentiating passive perineural invasion (PNI) from active tumor innervation. We examine how sympathetic signaling drives an "angio-metabolic switch" and immune evasion, whereas parasympathetic inputs exert context-dependent control over stemness and inflammation. We also highlight the underappreciated role of sensory neurons in promoting T-cell exhaustion via neuropeptides like calcitonin gene-related peptide (CGRP). Finally, we assess therapeutic strategies targeting neural dependence-from repurposing β-blockers to deploying nanotechnologies. Targeting neuro-tumor crosstalk offers a promising strategy to overcome therapeutic resistance and restore anti-tumor immunity.
Ma et al. (2026) studied this question.