bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2026–02–08
twelve papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis.
  2. Neuroinflammation and RAMP1: the Role of the Peripheral and Central Nervous System in Tumor Progression.
  3. The influence of neuro-tumor interactions on tumorigenesis and therapeutic response.
  4. Brain-cancer interactions outside the CNS.
  5. Neurotransmitters: Key regulators of the tumor immune microenvironment.
  6. Preoperative prediction of perineural invasion in intrahepatic cholangiocarcinoma with interpretable machine learning based on MRI.
  7. Noninvasive preoperative prediction of perineural invasion in intrahepatic cholangiocarcinoma based on dynamic contrast-enhanced MRI.
  8. The role of neurotransmitter signaling in colorectal cancer progression: Opportunities for drug repurposing.
  9. Breast Cancer Brain Metastases: Current Understanding and Future Directions.
  10. Pain signaling via sensory neurons drives breast cancer progression through neuropeptide release and κ-opioid counter-regulation.
  11. Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment.
  12. Neural-tumor crosstalk and molecular targeting: mechanisms and therapeutic implications in cancer neuroscience.
  1. Nature. 2026 Feb 04.
    Tumour-brain crosstalk restrains cancer immunity via a sensory-sympathetic axis.
    Haohan K Wei, Chuyue D Yu, Bo Hu, Xing Zeng, Hiroshi Ichise, Liang Li, Yu Wang, Ruiqi L Wang, Ronald N Germain, Rui B Chang, Chengcheng Jin.
      Body-brain communication has emerged as a key regulator of tissue homeostasis1-5. Solid tumours are innervated by different branches of the peripheral nervous system and increased tumour innervation is associated with poor cancer outcomes6-8. However, it remains unclear how the brain senses and responds to tumours in peripheral organs, and how tumour-brain communication influences cancer immunity. Here we identify a tumour-brain axis that promotes oncogenesis by establishing an immune-suppressive tumour microenvironment. Combining genetically engineered mouse models with neural tracing, tissue imaging and single-cell transcriptomics, we demonstrate that lung adenocarcinoma induces innervation and functional engagement of vagal sensory neurons, a major interoceptive system connecting visceral organs to the brain. Mechanistically, Npy2r-expressing vagal sensory nerves transmit signals from lung tumours to brainstem nuclei, driving elevated sympathetic efferent activity in the tumour microenvironment. This, in turn, suppresses anti-tumour immunity via β2 adrenergic signalling in alveolar macrophages. Disruption of this sensory-to-sympathetic pathway through genetic, pharmacological or chemogenetic approaches significantly inhibited lung tumour growth by enhancing immune responses against cancer. Collectively, these results reveal a bidirectional tumour-brain communication involving vagal sensory input and sympathetic output that cooperatively regulate anti-cancer immunity; targeting this tumour-brain circuit may provide new treatments for visceral organ cancers.
    DOI:  https://doi.org/10.1038/s41586-025-10028-8
  2. Cell Biochem Biophys. 2026 Feb 06.
    Neuroinflammation and RAMP1: the Role of the Peripheral and Central Nervous System in Tumor Progression.
    Pedro Daniel Moumesso Cavalcante, Jonas Lucas Dias da Silva, Laryssa Rosy Santos Oliveira, Rikelly Barbosa da Silva, Juliana Acioli Costa Lima, Guilherme de Brito Souza, Davi Ramon da Silva Santos, Júllia Victória Nascimento de Abrantes, Mateus Lima de Farias, Sofia Amancio de Almeida Oliveira, João Paulo Emiliano da Silva, Rafael de Oliveira Calaça Farias, Leonardo Prudêncio Coutinho de Almeida, Salomão Belfort Sparapan de Melo, Sandra Taveiros de Araújo, Raimundo Rodrigues de França-Júnior, José Emerson Xavier, Carlos Alberto de Carvalho Fraga.
      
    Keywords:  Calcitonin Gene-Related peptide; Cell proliferation; RAMP, neuroinflammation; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s12013-026-02009-z
  3. Exp Hematol Oncol. 2026 Feb 05. 15(1): 18
    The influence of neuro-tumor interactions on tumorigenesis and therapeutic response.
    Xiaokang Wang, Yuanliang Yan, Liugen Li, Tongfei Li, Abhimanyu Thakur, Kui Zhang, Juanni Li, Cheng Zhan, Hailin Tang, Zhijie Xu, Kuan Hu.
      The intricate crosstalk between the nervous system and tumors has emerged as a pivotal determinant of tumorigenesis, progression, and therapeutic response. This review synthesizes current insights into neuro-tumor interactions, highlighting how neuronal networks within the tumor microenvironment (TME) modulate cancer cell proliferation, invasion, and angiogenesis by releasing neurotransmitters, growth factors, etc. The neuro-immune axis, a critical interface linking neural signaling to immune regulation, is explored in depth, elucidating how neuronal-derived molecules influence the phenotype and function of immune cells (e.g., T cells, macrophages, natural killer (NK) cells) to affect anti-tumor immunity. In addition, the review also addresses neurotoxicity associated with tumor progression, particularly tumor-induced neuropathic pain, which arises from treatment-related injury. Finally, the therapeutic potential of targeting neural components in cancer is evaluated, including strategies to disrupt neuro-tumor communication (e.g., neurotransmitter receptor antagonists), modulate neuro-immune crosstalk, and alleviate treatment-related neurotoxicity. Overall, this review underscores the need to integrate neural signaling pathways into cancer biology and therapy, identifying unresolved issues in neuro-oncology and highlighting promising directions for developing neuro-targeted interventions to improve patient outcomes.
    Keywords:  Cancer neuroscience; Nerve-tumor interactions; Neuro-immune axis; Therapeutic implications; Tumor microenvironment
    DOI:  https://doi.org/10.1186/s40164-026-00752-w
  4. Oncogene. 2026 Feb 03.
    Brain-cancer interactions outside the CNS.
    Weihan Li, Ruixue Huo, Sailiang Liu, Kexin He, Hao Wu, Hao Wang, Shu-Heng Jiang, Junli Xue.
      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.
    DOI:  https://doi.org/10.1038/s41388-026-03684-1
  5. Semin Immunol. 2026 Jan 29. pii: S1044-5323(26)00002-3. [Epub ahead of print]81 102015
    Neurotransmitters: Key regulators of the tumor immune microenvironment.
    Liubo Zhang, Wei Jing, Yunbo Li, Yu Ping, Yi Zhang.
      Recent studies have revealed that neurotransmitters, as a class of important signaling molecules, have functional roles that extend beyond the traditional nervous system and play critical regulatory functions in the tumor immune microenvironment. Research has demonstrated that various classical neurotransmitters and their receptors are widely expressed in tumor tissues. Through complex receptor-mediated signaling networks, neurotransmitters dynamically regulate the functions of diverse cell types, including tumor cells and immune cells, thereby influencing tumor progression. Based on these discoveries, significant progress has been made in developing innovative drugs targeting neurotransmitter-receptor axes. Multiple agents, such as N-methyl-D-aspartate receptor (NMDAR), γ-aminobutyric acid-A (GABA-A) agonists, and dopamine receptor antagonists, have demonstrated promising antitumor effects in both preclinical studies and clinical trials. This review systematically summarizes the multidimensional regulatory mechanisms of neurotransmitters in tumor immunity and comprehensively discusses recent advances in neurotransmitter-targeted therapies. These findings not only provide a theoretical foundation for developing novel immunotherapeutic strategies based on neurotransmitter modulation but also open new research perspectives for understanding the emerging field of "neuro-immune-tumor" crosstalk.
    Keywords:  Neurotransmitter; Tumor immune microenvironment; Tumor immunology
    DOI:  https://doi.org/10.1016/j.smim.2026.102015
  6. Eur J Surg Oncol. 2026 Jan 28. pii: S0748-7983(26)00069-7. [Epub ahead of print]52(3): 111450
    Preoperative prediction of perineural invasion in intrahepatic cholangiocarcinoma with interpretable machine learning based on MRI.
    Xiaoqi Zhou, Meicheng Chen, Danyang Xu, Jing Hu, Ziwei Liu, Chenyu Song, Mimi Tang, Jifei Wang, Yuying Chen, Yanji Luo, Zhenpeng Peng, Shi-Ting Feng.
       INTRODUCTION: To develop radiomics and deep learning (DL) based interpretable models using MRI for preoperative prediction of perineural invasion (PNI) in intrahepatic cholangiocarcinoma (ICC).
    MATERIALS AND METHODS: A total of 165 pathologically confirmed ICC patients with preoperative MRI were retrospectively enrolled from two centers (center1, training set, n = 115; validation set, n = 14; internal test set, n = 15; center 2, external test set, n = 21). Radiomics and DL models were constructed for single-phase (pre-contrast, arterial phase, portal venous phase, hepatobiliary phase [HBP]) and multi-phase MRI using the Shukun AI platform and PNI-MambaNet. Model performance was evaluated with the area under the receiver operating characteristic curve (AUC). Gradient-weighted class activation mapping (Grad-CAM) heatmaps visualized the regions prioritized by the DL models.
    RESULTS: The PNI positive rate was 42.4 % (61/144) and 28.6 % (6/21) in the two centers. Radiomics HBP models achieved the highest AUC in the internal test set, while multi-phase model performed best in the external test set (AUC: HBP, 0.778 and 0.733 for the internal and external test sets, respectively; multi-phase, 0.759 and 0.778). For DL models, multi-phase model achieved the highest AUC in the internal test set, while HBP model performed best in the external test set (AUC: HBP, 0.926 and 0.856; multi-phase, 0.944 and 0.844). DL models outperformed radiomics models in the external test set, with Grad-CAM visualizing tumor margin regions as the interest area.
    CONCLUSIONS: DL models based on MRI effectively predict PNI in ICC, with visualizations enhancing clinical interpretability and potential application.
    Keywords:  Deep learning; Intrahepatic cholangiocarcinoma; Multi-phase MRI; Perineural invasion; Radiomics
    DOI:  https://doi.org/10.1016/j.ejso.2026.111450
  7. BMC Med Imaging. 2026 Feb 04.
    Noninvasive preoperative prediction of perineural invasion in intrahepatic cholangiocarcinoma based on dynamic contrast-enhanced MRI.
    Sisi Zhang, Yayuan Feng, Da He, Yuxian Wu, Ningyang Jia, Xingpeng Pan, Yiping Liu.
      
    Keywords:  Intrahepatic cholangiocarcinoma; Magnetic resonance imaging; Nomogram; Perineural invasion
    DOI:  https://doi.org/10.1186/s12880-026-02188-4
  8. Cytokine Growth Factor Rev. 2026 Jan 31. pii: S1359-6101(26)00018-3. [Epub ahead of print]88 88-104
    The role of neurotransmitter signaling in colorectal cancer progression: Opportunities for drug repurposing.
    He Jiang, Guangming Zhang, Wanjun Sun, Heng Zhang, Shiwu Zhang, Hui Wang.
      Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide, with treatment challenges often arising from drug resistance and the complexity of the tumor microenvironment (TME). Emerging evidence has repositioned the nervous system from a passive bystander to an active participant in cancer progression. Neurotransmitters, such as serotonin, glutamate, GABA, dopamine, acetylcholine, and norepinephrine, are now recognized as crucial regulators of CRC. They directly influence tumor cell proliferation, metastasis, stemness, and therapy resistance by activating their cognate receptors on cancer cells. Furthermore, they modulate the TME by affecting immune cells and stromal components. This intricate crosstalk presents a novel therapeutic avenue. Drug repurposing, the strategy of finding new uses for approved non-cancer drugs, offers a time-efficient and cost-effective path to translate these insights into clinical practice. A growing body of preclinical and clinical studies indicates that various psychoactive agents, including antidepressants, such as Selective Serotonin Reuptake Inhibitors, antipsychotics, anesthetics, and beta-blockers, exhibit potent anti-CRC effects. This review systematically summarizes the roles of key neurotransmitter systems in CRC pathogenesis and progression. It further explores the promising potential of repurposing existing neuropharmacological agents as novel therapeutic or adjunctive strategies for CRC, highlighting both the compelling opportunities and the challenges within this burgeoning field.
    Keywords:  Cancer neuroscience; Colorectal cancer; Drug repurposing; Neurotransmitter
    DOI:  https://doi.org/10.1016/j.cytogfr.2026.01.010
  9. Curr Oncol Rep. 2026 Feb 05. 28(1): 5
    Breast Cancer Brain Metastases: Current Understanding and Future Directions.
    Mohammad Alabdulrahman, Gordon R Daly, Sindhuja Naidoo, Lea Stuart, Sami Almasri, Ali Benour, Jason McGrath, Minatoullah Habaka, Gavin P Dowling, Cian M Hehir, Arnold Dk Hill, Damir Varešlija, Leonie S Young.
       PURPOSE OF REVIEW: To examine recent advances in understanding breast cancer brain metastases (BCBM), with emphasis on metastatic mechanisms, tumour-microenvironment interactions, receptor discordance between primary breast tumours and brain metastases, diagnostic innovations, and therapeutic strategies. The review sought to clarify how these developments inform precision management and identify priorities for future research.
    RECENT FINDINGS: Studies implicate JAK-STAT signalling, homologous recombination deficiency, c-MYC, PI3K/AKT/mTOR, and RET in BCBM progression. Tumour cells adapt via neuronal mimicry, metabolic reprogramming, and crosstalk with astrocytes and microglia. Receptor discordance between primary breast cancers and brain metastases occurs in up to one-third of cases and may alter systemic therapy. Emerging tools including liquid biopsy, spatial transcriptomics, and radiomics offer minimally invasive approaches for molecular profiling, spatial mapping, and imaging-based phenotyping to guide personalised management. Machine learning supports prognostication and imaging interpretation, though external validation is limited. BCBM reflect complex tumour-brain interactions. Advances in molecular understanding and diagnostics are beginning to inform the development of targeted therapies. Future work may benefit from integrating cancer neuroscience with computational modelling, standardise diagnostic platforms, and test the survival impact of receptor reassessment in prospective trials.
    Keywords:  Astrocyte-tumour interactions; Breast cancer brain metastases; C-MYC; Cancer neuroscience; HER3; Homologous recombination deficiency; JAK/STAT3; Liquid biopsies; Machine learning; PI3K/AKT/mTOR; RET; Radiomics; Receptor discordance; Spatial transcriptomics
    DOI:  https://doi.org/10.1007/s11912-026-01753-y
  10. Pharmacol Res. 2026 Jan 28. pii: S1043-6618(26)00028-9. [Epub ahead of print] 108113
    Pain signaling via sensory neurons drives breast cancer progression through neuropeptide release and κ-opioid counter-regulation.
    Hitoshi Makabe, Michiko Narita, Yasuyuki Nagumo, Masanori Fujiwara, Yusuke Hamada, Jion Takise, Takumi Yoshizawa, Sakura Sano, Shin Iizuka, Eri Asaba, Yukari Suda, Tomohisa Mori, Tsuyoshi Saitoh, Hiroshi Nagase, Vivianne L Tawfik, Shigehiro Yagishita, Akinobu Hamada, Kan Yonemori, Shin Takayama, Masayuki Yoshida, Ryo Yoshizawa, Kenichi Gn Suzuki, Rinshi S Kasai, Naoko Kuzumaki, Eriko Satomi, Minoru Narita.
      Severe pain in patients with breast cancer is associated with poorer survival outcomes, yet the mechanisms linking nociceptive signaling to tumor progression remain unclear. In a clinical cohort, breast cancer patients whose moderate or severe pain improved under specialized palliative care exhibited significantly longer survival than those with persistent pain. Serum levels of calcitonin gene-related peptide (CGRP) and substance P (SP), neuropeptides that can be released from sensory neurons, were elevated in breast cancer patients with uncontrolled pain, correlating positively with pain intensity and negatively with overall survival. In vitro, supernatants from depolarized human iPSC-derived sensory neurons containing CGRP, SP, and the endogenous κ-opioid receptor (KOR) ligand dynorphin attenuated docetaxel efficacy, promoted epithelial-mesenchymal transition, and enhanced migration in human triple-negative breast cancer (TNBC) cells, accompanied by Gi protein-coupled activation of the PI3K-Akt signaling pathway. In vivo, optogenetic activation of sensory neurons significantly accelerated tumor growth following orthotopic transplantation of murine TNBC cells, whereas combined blockade of CGRP and SP receptors suppressed this effect. Similarly, in patient-derived xenograft models of TNBC, dual receptor blockade effectively abrogated tumor progression. Conversely, in vitro treatment with dynorphin enhanced the cytotoxic efficacy of docetaxel, accompanied by the inhibition of PI3K-Akt signaling, whereas in vivo administration of the peripherally restricted KOR agonist nalfurafine methiodide markedly suppressed tumor growth. These findings establish a bidirectional neural-tumor axis in breast cancer progression. Therapeutically, combined blockade of CGRP/SP signaling with peripheral KOR agonism may present a novel strategy to enhance chemotherapy efficacy in TNBC patients.
    Keywords:  Breast cancer; CGRP; Neurogenic inflammation; Sensory neuron; Substance P; dynorphin; induced pluripotent stem cell (iPS)
    DOI:  https://doi.org/10.1016/j.phrs.2026.108113
  11. Cell. 2026 Feb 05. pii: S0092-8674(26)00048-6. [Epub ahead of print]
    Sensory neurons drive immune exclusion by stimulating a dense extracellular matrix in the breast cancer tumor microenvironment.
    Si-Wei Zhang, Han Wang, Yi Xiao, Luo-Tian Liu, Minhong Shen, Zhuang Wang, Shen Zhao, Xiao-Hong Ding, Ying Wang, Qing-Yuan Zhuang, Jinfei Ni, Zhi-Ming Shao, Yi-Zhou Jiang.
      Innervation is critical in tumor progression. However, the involvement of sensory neurons in the ecosystem of triple-negative breast cancer (TNBC) remains poorly elucidated. Here, we decipher that sensory neurons, the dominant neuron type in the TNBC ecosystem, drive the immune-excluded tumor microenvironment (TME) by stimulating a dense extracellular matrix. Mechanistically, a high concentration of nerve growth factor (NGF) in TME triggers sensory neurons to secrete the neuropeptide calcitonin gene-related peptide (CGRP), thereby activating cancer-associated fibroblasts (CAFs) to secrete collagen. Specifically, CGRP binds to its receptor RAMP1 (receptor activity modifying protein 1), which is expressed mainly on CAFs, and subsequently activates cyclic AMP (cAMP)/protein kinase A (PKA)/cAMP-response element binding protein 1 (CREB1) signaling to increase collagen deposition. Clinically, targeting sensory neurons remodels the disordered TME and synergizes with anti-programmed cell death protein 1 (PD-1) immunotherapy in TNBC. Collectively, our findings reveal a connection between sensory neurons and CAFs that obstructs antitumor immunity in TNBC. The CGRP antagonist rimegepant thus has clinical translational potential as an immuno-sensitizer to augment tumor immunotherapy.
    Keywords:  CGRP; breast cancer; cancer neuroscience; cancer-associated fibroblast; collagen; immunity; immunotherapy; innervation; sensory neuron; triple-negative breast cancer; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.cell.2026.01.001
  12. Cell Oncol (Dordr). 2026 Feb 02. 49(1): 35
    Neural-tumor crosstalk and molecular targeting: mechanisms and therapeutic implications in cancer neuroscience.
    Tianhui Hou, Huaze Ding, Guofang Huang, Tong Meng, Dianwen Song.
      
    DOI:  https://doi.org/10.1007/s13402-025-01151-9
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