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.
This review focuses on tumors arising outside the central nervous system and their bidirectional interactions with peripheral nerves, summarizing the current evidence on the molecular mechanisms underlying these reciprocal interactions.
It is proposed that the brain-tumor axis represents an emerging integrative hallmark of cancer, defined by the context-dependent duality of neural signaling, whereby identical pathways elicit opposing pro- or anti-tumorigenic effects contingent on tumor type, disease stage, and microenvironmental context.
Yu-Xin Liu, Chun-Yuan Guo, Xing Wang et al.· Cancer Treatment and Researc...· 0 citations
A hierarchical neuro–tumor interaction framework is proposed that provides an integrated conceptual basis for understanding the complexity and context dependency of neural regulation in cancer biology.
Current knowledge of neuronal regulation in cancer across three layers is summarized: direct synaptic communication, neuron-derived paracrine signaling, and neuroimmune modulation, and a translational framework is proposed to bridge basic discoveries with clinical application.
Shiyi Liu, C. Cao, Chang Zhu et al.· Biochimica et biophysica act...· 0 citations
This review synthesizes how nerves and brain activity directly influence tumour growth across multiple diseases—including gliomas, small cell lung cancer, breast cancer, pancreatic cancer, and prostate cancer—and how these neural signals converge with metabolic and drug-resistance pathways that limit the efficacy of co...
F. Petrelli, A. Callea, A. Ghidini et al.· Medical Oncology· 0 citations
This review critically evaluates the translational potential of targeting these neuro-immune interactions, highlighting combination strategies designed to enhance the efficacy of cancer immunotherapy.
Zhi-Fan Ran, Cheng-Hong Zeng, Jin-Li Han et al.· Frontiers in Immunology· 0 citations
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