劫持稳态：肿瘤恶液质中的脑-体神经回路与治疗机遇

Hijacking homeostasis: brain-body neural circuits in cancer cachexia and therapeutic opportunities

摘要

肿瘤恶液质是一种多因素综合征，其特征是进行性骨骼肌消耗（伴或不伴脂肪组织减少），且无法通过常规营养支持完全逆转。传统观点将其视为由肿瘤诱导的全身性炎症和代谢紊乱驱动的外周性疾病，而最新证据表明，中枢神经系统（尤其是下丘脑）已成为肿瘤介导全身失调的关键靶点。本综述提出一种“稳态劫持”模型，系统阐述肿瘤如何通过释放外泌体、炎症因子和代谢物等信号分子，劫持脑-体神经回路，从而重编程能量分配与摄食行为，最终驱动肿瘤恶液质的恶性循环。本研究从“脑-体”（中枢指令失调）与“体-脑”（外周信号反馈）两个相互关联的维度，解析肿瘤恶液质背后的神经-免疫-代谢机制，并前瞻性探讨针对脑-体接口的新型治疗策略。

Abstract

Cancer cachexia is a multifactorial syndrome characterized by progressive skeletal muscle wasting (with or without loss of adipose tissue) that cannot be fully reversed by conventional nutritional support. Traditionally viewed as a peripheral disorder driven by tumor-induced systemic inflammation and metabolic dysregulation, emerging evidence now highlights the central nervous system, particularly the hypothalamus, as a pivotal target in tumor-mediated systemic disruption. This review proposed a "homeostatic hijacking" model, systematically elaborating on how tumors release signaling molecules—such as exosomes, inflammatory cytokines and metabolites—to hijack brain-body neural circuits, thereby reprogramming energy allocation and feeding behavior, and ultimately driving the vicious cycle of cachexia. We analyzed the neuroimmuno-metabolic mechanisms underlying cachexia from two interconnected dimensions: "brain-to-body" (central command dysregulation) and "body-to-brain" (peripheral signal feedback). Furthermore, we prospectively discussed novel therapeutic strategies targeting the brain-body interface, offering a refreshed framework for intervening in this intractable syndrome.

关键词

肿瘤恶液质 / 脑-体互作 / 神经回路 / 下丘脑 / 稳态劫持 / 治疗靶点

Key words

cancer cachexia / brain-body interaction / neural circuits / hypothalamus / homeostatic hijacking / therapeutic targets

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基金资助

兰州大学第一医院高层次人才引进基金()