Neurological regulation of tumors: An interdisciplinary frontier from circuit mechanisms to targeted intervention

Traditional oncology research has long focused on genetic, immunological, and vascular mechanisms. In recent years, with the deepening interdisciplinary convergence, “cancer neuroscience” has rapidly emerged as a cutting-edge field for deciphering the mechanisms of tumor initiation and progression. In this article, we systematically review the research trajectory of neural-tumor interactions: from the early observations of neural infiltration within tumors to recent breakthroughs revealing that the nervous system actively regulates tumor processes through multiple mechanisms. In intracranial tumors, glioma cells can form functional synapses with neurons, "hijacking" neural signals such as glutamate to drive their own proliferation. In peripheral solid tumors, specific brain circuits (e. g., the amygdala-sympathetic nerve pathway) can remotely regulate the progression of cancers such as breast cancer; meanwhile, sympathetic, parasympathetic, and sensory nerves directly act on tumor cells or reshape the immune microenvironment through releasing neurotransmitters and neuropeptides, such as norepinephrine, acetylcholine, and calcitonin gene-related peptide (CGRP), thereby influencing tumor evolution. These findings collectively constitute a "neuro-immune-tumor" regulatory axis, providing a novel perspective for understanding tumor biology. Building upon our group's previous work, we propose that the nervous system represents an indispensable and active component of the tumor microenvironment, extensively participating in tumor initiation, progression, metastasis, and immune regulation through multi-level mechanisms involving electrical signals, chemical neurotransmitters, and neural circuits. Targeting neural-tumor interactions (e. g., using β-blockers or modulating specific neural circuits) has already demonstrated significant translational potential for synergizing with existing therapies. Through integrating key advances in this field, we systematically elaborate the translational pathway from basic discoveries to clinical exploration, analyze current technical and clinical challenges, and prospect a forward-looking perspective on interdisciplinary collaboration and precision intervention, thereby, providing theoretical reference and framework for deepening the understanding of systemic tumor regulation and developing novel neuro-targeted therapeutic strategies.