Entangled cellular and molecular relationships at the sensory neuron-cancer interface

Debpali Sur¹, Yi Zeng², Hiroki Kobayashi², Xiaofei Zhi³, Mara R Goetz⁴, Clara M Müller⁵, Anastasia-Maria Zavitsanou⁶, Caroline C Picoli⁷, Andre A Martel Matos⁸, Javier Pareja⁹, Brajesh K Savita¹, Taeho Lee¹, Jair P Cunha-Junior¹⁰, Jaime Henrique Amorim¹¹, Amin Reza Nikpoor¹², Alissa Dory¹², Ajitha Thanabalasuriar¹³, Pedro A F Galante¹⁴, Vincent T Ma¹⁵, Aaron W James¹⁶, Andrew J Shepherd¹⁷, Madeleine J Oudin¹⁸, Yuri L Bunimovich¹⁹, Nicole N Scheff⁸, Nisha J D'Silva²⁰, Karen O Dixon⁹, Ishmail Abdus-Saboor⁶, Timothy C Wang², Sebastien Talbot²¹, Alexander Birbrair²²

Affiliations

¹ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA.
² Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
³ Department of GI Surgery, Affiliated Hospital of Nantong University, Nantong, China.
⁴ Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁶ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Biological Sciences, Columbia University, New York, NY, USA.
⁷ MaineHealth Institute for Research, Scarborough, ME, USA.
⁸ Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹ Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
¹⁰ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Department of Immunology, Federal University of Uberlândia, Uberlândia, Brazil.
¹¹ Center of Biological Sciences and Health, Federal University of Western Bahia, Barreiras, Brazil.
¹² Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
¹³ Department of Physiology and Pharmacology, McGill University, São Paulo, Brazil.
¹⁴ Centro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo, Brazil.
¹⁵ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Department of Medicine, Division of Hematology, Medical Oncology, and Palliative Care, University of Wisconsin-Madison, Madison, WI, USA.
¹⁶ Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
¹⁷ Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁸ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
¹⁹ Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
²⁰ Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
²¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada; Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden. Electronic address: sebastien.talbot@ki.se.
²² Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: birbrair@wisc.edu.

PMID: 40907473
DOI: 10.1016/j.neuron.2025.07.017

Review

Entangled cellular and molecular relationships at the sensory neuron-cancer interface

Debpali Sur et al. Neuron. 2025.

. 2025 Sep 3;113(17):2760-2790.

doi: 10.1016/j.neuron.2025.07.017.

Authors

Affiliations

¹ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA.
² Division of Digestive and Liver Disease, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA.
³ Department of GI Surgery, Affiliated Hospital of Nantong University, Nantong, China.
⁴ Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany; Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁵ Department of Surgery, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany.
⁶ Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY, USA; Department of Biological Sciences, Columbia University, New York, NY, USA.
⁷ MaineHealth Institute for Research, Scarborough, ME, USA.
⁸ Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA; Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
⁹ Department of Biomedicine, University of Basel and University Hospital of Basel, Basel, Switzerland.
¹⁰ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Department of Immunology, Federal University of Uberlândia, Uberlândia, Brazil.
¹¹ Center of Biological Sciences and Health, Federal University of Western Bahia, Barreiras, Brazil.
¹² Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
¹³ Department of Physiology and Pharmacology, McGill University, São Paulo, Brazil.
¹⁴ Centro de Oncologia Molecular, Hospital Sirio-Libanes, São Paulo, Brazil.
¹⁵ Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Department of Medicine, Division of Hematology, Medical Oncology, and Palliative Care, University of Wisconsin-Madison, Madison, WI, USA.
¹⁶ Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.
¹⁷ Department of Symptom Research, Division of Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
¹⁸ Department of Biomedical Engineering, Tufts University, Medford, MA, USA.
¹⁹ Department of Dermatology, University of Pittsburgh, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
²⁰ Department of Pathology, Medical School, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
²¹ Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada; Department of Physiology and Pharmacology, Karolinska Institute, Solna, Sweden. Electronic address: sebastien.talbot@ki.se.
²² Department of Dermatology, University of Wisconsin-Madison, Madison, WI, USA; Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USA; Department of Cell and Regenerative Biology, University of Wisconsin-Madison, Madison, WI, USA. Electronic address: birbrair@wisc.edu.

PMID: 40907473
DOI: 10.1016/j.neuron.2025.07.017

Erratum in

Entangled cellular and molecular relationships at the sensory neuron-cancer interface.
Sur D, Zeng Y, Kobayashi H, Zhi X, Goetz MR, Müller CM, Zavitsanou AM, Picoli CC, Martel Matos AA, Pareja J, Savita BK, Lee T, Cunha-Junior JP, Amorim JH, Nikpoor AR, Dory A, Thanabalasuriar A, Galante PAF, Ma VT, James AW, Shepherd AJ, Oudin MJ, Bunimovich YL, Scheff NN, D'Silva NJ, Dixon KO, Abdus-Saboor I, Wang TC, Talbot S, Birbrair A. Sur D, et al. Neuron. 2025 Oct 15;113(20):3491. doi: 10.1016/j.neuron.2025.09.030. Epub 2025 Sep 27. Neuron. 2025. PMID: 41016393 No abstract available.

Abstract

Peripheral sensory neurons, once regarded merely as a passive route for nociceptive signals, are now acknowledged as active participants in solid tumor progression. This review explores how sensory neurons influence and are influenced by the tumor microenvironment (TME) through both chemical and electrical signaling, underscoring their pivotal role in the emerging field of cancer neuroscience. We summarize recent findings indicating that cancer-neuron interactions vary among different organs and experimental models, highlighting the ways in which various tumors recruit and reprogram sensory neurons to establish mutual communication loops that foster malignancy. Clinically, the degree of sensory innervation and the level of neuropeptide signaling show promise as diagnostic and prognostic biomarkers, while targeting these pathways may enhance the efficacy of standard cancer treatments. This review also highlights current knowledge gaps and proposes future research directions aimed at disrupting sensory neuron-tumor interactions, with the ultimate goal of improving clinical outcomes across multiple cancer types.

Keywords: cancer neuroscience; cancer progression; context-dependent roles; sensory neurons; tumor microenvironment.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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Entangled cellular and molecular relationships at the sensory neuron-cancer interface

Affiliations

Entangled cellular and molecular relationships at the sensory neuron-cancer interface

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

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LinkOut - more resources

Full Text Sources

Medical