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\nCancer Neuroscience: Decoding Neural Circuitry in Tumor Evolution for Targeted Therapy  \nMengyu Yuan, Rongjiao Xi, Yong Kang,* Ming-jie Kuang,* and Xiaoyuan Ji*  \nRecent breakthroughs in tumor biology have redefined the tumor microenvironment as a dynamic ecosystem in which the nervous system has emerged as a pivotal regulator of oncogenesis. In addition to their classical developmental roles, neural‒tumor interactions orchestrate a sophisticated network that drives cancer initiation, stemness maintenance, metabolic reprogramming, and therapeutic evasion. This crosstalk operates through multimodal mechanisms, including paracrine signaling, electrophysiological interactions, and structural innervation guided by axon-derived guidance molecules. Key discoveries reveal that tumors actively recruit and remodel local neurons, hijacking neurodevelopmental pathways to foster invasive growth. Moreover, malignant cells exhibit neuronal-like plasticity, adopting electrophysiological properties that increase survival under therapeutic stress. These findings position neural mimicry as a hallmark of aggressive cancers. The expanding field of cancer neuroscience seeks to unravel the essential signaling factors that drive the complex communication between cancer and the nervous system, utilizing these findings to enhance precision therapies for cancer management. In this Review, we highlight considerable advancementsin cancer neuroscience studies, sparking further discussions on various research possibilities and outlining a direction for future investigations. Additionally, we explored promising therapeutic strategies rooted in neural–tumor interactions that could synergize with conventional standard treatments, offering renewed therapeutic vigor for many refractory malignancies.  \n1. Introduction  \nThroughout the entirety of life, the nervous system, which is essential for all physiological functions of the organ system, orchestrates the development of tissues and organs, maintains homeostasis, and regulates plasticity and regeneration. Despite its extensive and pivotal role within the human body, the important role of the nervous system in cancer has long been overlooked. Its branches pervade the entire body, often accompanying the microvasculature and penetrating nearly all tissue microenvironments, saving the epidermis. Similarly, this dense neural innervation reaches the tumor microenvironment, significantly impacting cancer through mechanisms such as paracrine signaling and electrochemical communication. Thus, the nervous system may play a critical role in various cancers, influencing their onset and progression. Conversely, tumors can reshape neural circuits, potentially causing neurological dysfunctions that further exacerbate cancer progression, creating a vicious cycle. [1] Recent studies have increasingly highlighted a profound connection between the nervous system and cancer, giving rise to the field of cancer  \nM. Yuan, R. Xi, Y. Kang, X. Ji  \nState Key Laboratory of Advanced Medical Materials and Devices Medical College, Tianjin University  \nTianjin 300072, China  \nE-mail: [kangyong@tju.edu.cn](kangyong@tju.edu.cn); [jixiaoyuan@tju.edu.cn](jixiaoyuan@tju.edu.cn)  \nM.-jie Kuang  \nDepartment of Orthopedics  \nShandong Provincial Hospital Affiliated to Shandong First Medical University  \nJinan, Shandong 250021, China  \nE-mail: [doctorkmj@tmu.edu.cn](doctorkmj@tmu.edu.cn)  \nThe ORCID identification number(s) for the author(s) of this article  \ncan be found under [https://doi.org/10.1002/advs.202506813](https://doi.org/10.1002/advs.202506813)[ ](https://doi.org/10.1002/advs.202506813)© 2025 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.  \nDOI: 10.1002/advs.202506813  \nneu","cbCaidqPFGqNhR0G","https://ap.wps.com/l/cbCaidqPFGqNhR0G","pdf",14031108,24,"English","# Introduction\n## Neural system roles in cancer and homeostasis\n## Tumor-driven remodeling of neural circuits\n## Host and neural components of the tumor microenvironment\n## Progress and future directions in cancer neuroscience","[{\"question\":\"How does the nervous system influence cancer development and progression?\",\"answer\":\"The nervous system affects cancer onset and progression by shaping interactions within the tumor microenvironment, including paracrine signaling and electrochemical communication.\"},{\"question\":\"What mechanisms enable neural–tumor crosstalk?\",\"answer\":\"Neural–tumor crosstalk occurs through multimodal pathways such as paracrine signaling, electrophysiological interactions, and structural innervation guided by axon-derived guidance molecules.\"},{\"question\":\"Why are neural interactions important for targeted therapy?\",\"answer\":\"Neural–tumor interactions can promote therapeutic evasion and survival under treatment stress, making neural mimicry and neural recruitment relevant for developing precision therapies and synergistic treatment strategies.\"}]","Cancer Neuroscience - Decoding Neural Circuitry in Tumor Evolution for Targeted Therapy | PDF",1790200449]