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This paradigm builds upon two centuries of observations, from Cruveilhier's 19th-century documentation of perineural invasion to contemporary single-cell analyses demonstrating how neurons dynamically orchestrate tumorigenesis through three principal mechanisms: (1) synaptic neurotransmitter release (e.g., norepinephrine, glutamate) [2], (2) guided metastatic spread via axon pathfinding molecules [3], and (3) creation of immunosuppressive niches through neuroimmune crosstalk (Fig

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