ABSTRACT Cancer neuroscience has emerged as a paradigm‐shifting discipline that reveals the active role of the nervous system in tumor development and progression. This review synthesizes current understanding of how bidirectional interactions between neurons and cancer cells influence tumorigenesis, metastasis, and therapy response. While earlier frameworks have established the fundamental mechanisms of nerve–tumor interactions, the present study proposes an expanded classification scheme that incorporates two additional mechanisms: perineural invasion as a unique metastatic pathway and neuro‐microbic‐oncology, which incorporates the gut–brain–immune axis into cancer biology. The remodeling of tumor microenvironment is structured around three principal mechanisms: electrochemical signaling, paracrine communication, and neuroimmune modulation. The contribution of these interactions to cancer‐associated comorbidities, including pain, cachexia, and cognitive dysfunction, is highlighted, and their translational relevance is discussed in the context of emerging neurotherapeutic strategies. This review provides an integrated conceptual framework that connects neurobiology, oncology, and immunology, thereby informing the development of nerve‐targeted therapeutic strategies with potential to improve clinical outcomes in cancer.
Wang et al. (2026) studied this question.