Tumor-nerve interactions in cancer regulation and progression

Jianyi Zhao; Lilin Cheng; Jian Yang; Feifei Xu; Weixiang Qi; Keman Liao; Li Zhou; Lu Cao; Jiayi Chen; Yingying Lin

doi:10.1016/j.canlet.2025.217483

Tumor-nerve interactions in cancer regulation and progression

Cancer Lett. 2025 Jan 20:612:217483. doi: 10.1016/j.canlet.2025.217483. Online ahead of print.

Authors

Jianyi Zhao¹, Lilin Cheng², Jian Yang³, Feifei Xu¹, Weixiang Qi¹, Keman Liao¹, Li Zhou¹, Lu Cao⁴, Jiayi Chen⁵, Yingying Lin⁶

Affiliations

¹ Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Proton-Therapy, Shanghai, 201801, China.
² Department of Neurosurgery, Changhai Hospital, Naval Medical University, Shanghai, 200433, China.
³ Department of Neurosurgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200127, China.
⁴ Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Proton-Therapy, Shanghai, 201801, China. Electronic address: cl11879@rjh.com.cn.
⁵ Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Proton-Therapy, Shanghai, 201801, China. Electronic address: cjy11756@rjh.com.cn.
⁶ Department of Radiation Oncology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China; Shanghai Key Laboratory of Proton-Therapy, Shanghai, 201801, China. Electronic address: yylin@sibs.ac.cn.

PMID: 39842496
DOI: 10.1016/j.canlet.2025.217483

Abstract

Tumor-nerve interactions play a critical role in tumor progression, metastasis, and treatment resistance, redefining our understanding of the tumor microenvironment. This review provides a comprehensive analysis of how the peripheral and central nervous systems contribute to cancer biology, focusing on mechanisms of neural invasion, immune evasion, and tumor adaptation. It has highlighted the emerging potential of repurposing nervous system-targeted drugs originally developed for neurodegenerative and autoimmune diseases as innovative cancer therapies. The review also addresses key challenges, including the limitations of current experimental models and the complexity of translating preclinical findings to clinical applications. By bridging the gap between neuroscience and oncology, this interdisciplinary study aims to discover novel therapeutic strategies to improve outcomes for cancer patients.

Keywords: Cancer neuroscience; Crosstalk; Tumor microenvironment; Tumor-nerve interactions.