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Review

Regulation of solid tumors by the peripheral nervous system.

Jul 2026 · Journal of Experimental Medicine · Vol 223 8 · 0 citations · 107 references
Medicine

TL;DR

The nervous system is identified as an upstream regulator of cancer biology and a tractable target for intervention by synthesizing mechanistic insights into how the peripheral nervous system shapes the tumor microenvironment to influence tumor behavior and highlighting emerging therapeutic opportunities to target neural pathways.

Abstract

The nervous system has emerged as a critical regulator of cancer progression. Recent studies demonstrate that peripheral neurons shape tumor growth, dissemination, and therapeutic response by regulating multiple components of the tumor microenvironment. In parallel, tumors within the body remodel their neural niche by recruiting innervation and modulating neuronal phenotype and activity. This bidirectional cross talk positions neural circuits as integral components of the tumor ecosystem, linking environmental cues, including metabolic stress, inflammation, and the impact of treatment, to coordinated multicellular responses that promote progression and treatment resistance. Here, we review the field of cancer neuroscience with a focus on solid tumors originating outside the central nervous system. We synthesize mechanistic insights into how the peripheral nervous system shapes the tumor microenvironment to influence tumor behavior and highlight emerging therapeutic opportunities to target neural pathways. Together, these findings identify the nervous system as an upstream regulator of cancer biology and a tractable target for intervention.

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