Xiaokang Wang, Yuanliang Yan, Liugen Li, Tongfei Li, Abhimanyu Thakur, Kui Zhang, Jie Li, Cheng Zhan, Hailin Tang, Zhijie Xu, Kuan Hu
The intricate crosstalk between the nervous system and tumors has emerged as a pivotal determinant of tumorigenesis, progression, and therapeutic response. This review synthesizes current insights into neuro-tumor interactions, highlighting how neuronal networks within the tumor microenvironment (TME) modulate cancer cell proliferation, invasion, and angiogenesis by releasing neurotransmitters, growth factors, etc. The neuro-immune axis, a critical interface linking neural signaling to immune regulation, is explored in depth, elucidating how neuronal-derived molecules influence the phenotype and function of immune cells (e.g., T cells, macrophages, natural killer (NK) cells) to affect anti-tumor immunity. In addition, the review also addresses neurotoxicity associated with tumor progression, particularly tumor-induced neuropathic pain, which arises from treatment-related injury. Finally, the therapeutic potential of targeting neural components in cancer is evaluated, including strategies to disrupt neuro-tumor communication (e.g., neurotransmitter receptor antagonists), modulate neuro-immune crosstalk, and alleviate treatment-related neurotoxicity. Overall, this review underscores the need to integrate neural signaling pathways into cancer biology and therapy, identifying unresolved issues in neuro-oncology and highlighting promising directions for developing neuro-targeted interventions to improve patient outcomes.