Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives

Sep 22, 2026

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Lung cancer remains a leading cause of cancer-related deaths worldwide. Despite advances in targeted therapy and immunotherapy, tumor heterogeneity and the tumor microenvironment often limit treatment outcomes. This review describes bidirectional nervous system–cancer interactions and explains how psychological stress, sleep disorders, and smoking act through neuroendocrine–immune networks to affect lung cancer initiation and progression. It also summarizes context-dependent neurotransmitter effects and evaluates neuromodulatory therapeutic potential, highlighting gaps between clinical evidence and preclinical findings.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages29

Reading Time1 h 13 min

AccessFree to download

Abstract

Nervous system–cancer interactions

Neuroendocrine–immune network regulation

Dual roles of key neurotransmitters

Therapeutic potential of neuromodulatory agents

Challenges and future directions

Clinical and Experimental Medicine (2026) 26:299 [https://doi.org/10.1007/s10238-026-02278-1](https://doi.org/10.1007/s10238-026-02278-1) REVIEW Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives Junfeng Zhao1,2 · Yiming Han3 · Yongxue Li4 · Ying Li5,6 · Yiheng Sun3 · Yingrui Bai7 · Jiaxuan Chen8 · Chuankun Han8 · YifeiYan8 · Chen Zhou8 · Chengxin Liu1 Received: 22 May 2026 / Accepted: 26 July 2026 © The Author(s) 2026 Abstract Lung cancer remains a leading cause of cancer-related deaths worldwide. Despite advances in targeted therapy and immunotherapy, treatment outcomes are often constrained by tumor heterogeneity and the complex tumor microenvironment. Recent studies highlight the critical role of the nervous system in lung cancer pathogenesis through bidirectional interactions between the central/peripheral nervous system and cancer cells. This review systematically explores how psychological stress, sleep disorders, and smoking influence the initiation and progression of lung cancer via neuroendocrineimmune networks. We further detail the dual roles of key neurotransmitters—including catecholamines, GABA, serotonin, dopamine, glutamate, histamine, and acetylcholine—in regulating tumor proliferation, epithelial-mesenchymal transition, angiogenesis, and immune evasion, with an emphasis on their context-dependent and receptor subtype-specific effects. Emerging evidence indicates that neurotransmitters remodel the tumor microenvironment by modulating immune cell function and receptor-mediated signaling pathways. We also discuss the therapeutic potential of neuromodulatory agents, particularly β-blockers and neurotransmitter receptor-targeted drugs, and their possible synergistic effects with conventional therapies, while critically distinguishing between strategies supported by clinical evidence and those remaining atthe preclinical stage. Challenges persist, including neurotransmitter concentration gradients, receptor subtype specificity, and limitations of preclinical models. The convergence of neuroscience and oncology offers promising avenues for innovative lung cancer therapies, underscoring the necessity for interdisciplinary collaboration to translate these discoveries into clinical practice. Junfeng Zhao, Yiming Han and Yongxue Li contributed equally to this work. Chengxin Liu [cxliu@email.sdfmu.edu.cn](cxliu@email.sdfmu.edu.cn) 1 Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan 250000, Shandong, China 2 Department of Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, Sichuan, China 3 Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 4 Affiliated Hospital of Qingdao University, Qingdao, China 5 Department of Respiratory Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan 250000, Shandong, China 6 Division of Thoracic Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, Sichuan, China 7 School of Clinical Medicine, Shandong Second Medical University, Weifang 261053, Shandong, China 8 Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan 250000, Shandong, China Graphical abstract Keywords Lung cancer · Neurotransmitters · Immune · Tumor microenvironment Abbreviations 5-HT 5-HTRACh AChR ADRB2 ADRB3 AI ALDH AMPK AR bsAbs CA12 CAR CASZ1 CCL2 CD8 CEA CHRNA5 CI CLOCK CNNs CNS 5-Hydroxytryptamine 5-Hydroxytryptamine Receptor Acetylcholine Acetylcholine Receptor Beta-2 Adrenergic Receptor Beta-3 Adrenergic Receptor Artificial Intelligence Aldehyde Dehydrogenase AMP-activated Protein Kinase Adrenergic Receptor Bispecific Antibodies Carbonic Anhydrase 12 Carvedilol Castor Zinc Finger 1 C

FAQs

How does the nervous system influence lung cancer development according to the review?

The review emphasizes bidirectional interactions between the central/peripheral nervous system and lung cancer cells. These interactions link neurobiology with tumor initiation and progression.

Which factors are discussed as influencing lung cancer through neuroendocrine–immune networks?

Psychological stress, sleep disorders, and smoking are discussed as influencing lung cancer via neuroendocrine–immune networks. These factors shape disease initiation and progression.

What is the therapeutic focus of the review on neuromodulatory agents?

It discusses the therapeutic potential of neuromodulatory agents, especially β-blockers and neurotransmitter receptor-targeted drugs. It also considers possible synergistic effects with conventional therapies.

Sep 22, 2026

Upload by nayy☆