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Cancer cells establish tumorspecific neural networks within tumor tissues via neurotrophic hijacking. The nervous system regulates tumor initiation, progression, and metastasis either directly by regulating signal transduction in tumor cells or indirectly by modulating the tumor microenvironment (TME). The positive feedback loop between cancer cells and nerves promotes tumor progression. Deciphering the regulatory role of nerves in tumor progression may yield novel anticancer therapeutic options. In this review, the interaction between nerves and cancer cells is described, including how cancer cells hijack and remodel nervous system structure and function, and how neuron\u2010signaling regulates cancer cell growth directly or indirectly through modulating the TME. This evidence of the critical role of nerves in the malignant phenotype of tumors indicates the potential of using neuron\u2010signaling targeting strategies in cancer treatment. 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