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Brain-cancer interactions outside the CNS

Oncogene (2026)Cite this article

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Abstract

Emerging research highlights the key role of the central nervous system in regulating peripheral tumor progression via neural, neuroendocrine, and immune pathways. Although direct evidence linking the brain to peripheral tumor initiation remains limited, recent studies using retrograde tracing have revealed anatomical and functional circuits between specific brain regions and peripheral solid tumors. These circuits influence malignant, stromal, and immune cells within the tumor microenvironment, as well as systemic immune and metabolic processes. In this review, we synthesize current findings on brain-periphery neural networks across multiple cancer types and discuss how tumor burden can reshape brain activity, contributing to emotional and cognitive disturbances, and how the brain, in turn, regulates tumor biology. In particular, we address the translational potential of targeting brain-tumor circuits via neuromodulation, behavioral interventions, and lifestyle-based therapies. Understanding these bidirectional communications offers new approaches for systemic, integrative therapeutic strategies.

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Fig. 1: Overview of the intricate relationships between brain and periphery.
Fig. 2: CNS regulation of cancer and related diseases.
Fig. 3: CNS innervation of peripheral solid tumors and cancer-related CNS alterations.

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Authors and Affiliations

  1. Department of Oncology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, PR China

    Weihan Li, Ruixue Huo, Kexin He, Hao Wu & Junli Xue

  2. Department of Ultrasound, Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China

    Sailiang Liu

  3. Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, PR China

    Hao Wang

  4. State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, PR China

    Shu-Heng Jiang

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Contributions

These authors contributed equally: Weihan Li, Ruixue Huo, and Sailiang Liu. WHL, RXH, SLL and KXH wrote and edited the manuscript. WHL, Hao Wu and Hao Wang produced the figures and illustrations. SHJ and JLX contributed text and references, critically reviewed and edited the manuscript. All authors discussed the ideas and searched the literature for relevant publications supporting the concepts reviewed in this manuscript.

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Li, W., Huo, R., Liu, S. et al. Brain-cancer interactions outside the CNS. Oncogene (2026). https://doi.org/10.1038/s41388-026-03684-1

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