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神经系统调控肿瘤:从环路机制到靶向干预的交叉前沿OA

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

中文摘要英文摘要

传统肿瘤学研究长期聚焦于遗传、免疫与血管机制.近年来,随着多学科深度交叉,"癌症神经科学"迅速崛起,成为揭示肿瘤发生发展机制的前沿领域.本文系统梳理了神经-肿瘤互作的研究脉络:从早期观察到的肿瘤神经浸润现象,到近年突破性发现——神经系统通过多种机制主动调控肿瘤进程.在颅内肿瘤中,胶质瘤细胞可与神经元形成功能性突触,"劫持"谷氨酸等神经信号以驱动自身增殖;在外周实体瘤中,大脑特定神经环路(如杏仁核-交感神经通路)能够远程调控乳腺癌等进展;同时,交感、副交感和感觉神经通过释放去甲肾上腺素、乙酰胆碱、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)等递质与神经肽,直接作用于肿瘤细胞或通过重塑免疫微环境影响肿瘤演进.这些发现共同构成了"神经-免疫-肿瘤"调控轴,为理解肿瘤生物学提供了全新视角.结合本课题组既往工作,我们认为:神经系统是肿瘤微环境中不可或缺的活跃组分,通过电信号、化学递质及神经环路等多层次方式,广泛参与肿瘤发生、发展、转移及免疫调节.靶向神经-肿瘤互作(如应用β受体阻滞剂、调控特定神经环路等)已展现出协同现有疗法的显著转化潜力.本述评通过整合该领域关键进展,系统阐述了从基础发现到临床探索的转化路径,剖析了当前面临的技术与临床挑战,并对跨学科合作与精准干预的未来方向进行展望,从而为深化理解肿瘤系统性调控机制、开拓神经靶向治疗新策略提供理论参考与框架指引.

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.

张毅;熊斯怡

陆军军医大学第一附属医院乳腺甲状腺外科,重庆市卫生健康委员会乳腺癌微创与精准诊疗重点实验室,重庆陆军军医大学第一附属医院乳腺甲状腺外科,重庆市卫生健康委员会乳腺癌微创与精准诊疗重点实验室,重庆

医药卫生

癌症神经科学神经系统肿瘤肿瘤微环境神经-免疫

cancer neurosciencenervous systemtumortumor microenvironmentneuroimmunity

《陆军军医大学学报》 2026 (6)

663-669,7

国家自然科学基金(82403678),重庆市自然科学基金重点项目(CSTB2023NSCQ-ZDX0002),重庆市重大医学研究计划(重庆市卫生健康委与科技局联合项目,2024DBXM001) Supported by the National Natural Science Foundation of China(82403678),the Key Project of Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDX0002)and the Project of Major Medical Research Plan of Chongqing(Joint Project of Chongqing Health Commission and Chongqing Science and Technology Commission,2024DBXM001).

10.16016/j.2097-0927.202601070

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