bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2025–09–14
six papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis.
  2. Cancer Neuroscience: Decoding Neural Circuitry in Tumor Evolution for Targeted Therapy.
  3. Next-gen tools in cancer neuroscience.
  4. Vitamin D Binding Protein, a Ligand of Integrin beta 1, Motivates Both Tumor Cells and Schwann Cells to Promote Perineural Invasion in Pancreatic Ductal Adenocarcinoma.
  5. Identification of key genes associated with perineural invasion in stage II colorectal cancer and their prognostic implications.
  6. Unraveling the nexus in the neuro-neoplastic progression of colorectal cancer: Potential role of β2-adrenergic receptor (β2-AR).
  1. Nature. 2025 Sep 10.
    Neuronal activity-dependent mechanisms of small cell lung cancer pathogenesis.
    Solomiia Savchuk, Kaylee M Gentry, Wengang Wang, Elana Carleton, Carlos A O Biagi-Junior, Karan Luthria, Belgin Yalçın, Lijun Ni, Hannah C Farnsworth, Rachel A Davis, Richard Drexler, Johannes C Melms, Yin Liu, Lehi Acosta-Alvarez, Griffin G Hartmann, Elisa C Pavarino, Jenna LaBelle, Pamelyn J Woo, Angus M Toland, Fangfei Qu, Yoon Seok Kim, Mariella G Filbin, Mark A Krasnow, Keith L Ligon, Benjamin Izar, Julien Sage, Bernardo L Sabatini, Michelle Monje, Humsa S Venkatesh.
      Neural activity is increasingly recognized as a crucial regulator of cancer growth. In the brain, neuronal activity robustly influences glioma growth through paracrine mechanisms1 and by electrochemical integration of malignant cells into neural circuitry via neuron-to-glioma synapses2,3. Outside of the central nervous system, innervation of tumours such as prostate, head and neck, breast, pancreatic, and gastrointestinal cancers by peripheral nerves similarly regulates cancer progression4-12. However, the extent to which the nervous system regulates small cell lung cancer (SCLC) progression, either in the lung or when growing within the brain, is less well understood. SCLC is a lethal high-grade neuroendocrine tumour that exhibits a strong propensity to metastasize to the brain. Here we demonstrate that in the lung, vagus nerve transection markedly inhibits primary lung tumour development and progression, highlighting a critical role for innervation in SCLC growth. In the brain, SCLC cells co-opt neuronal activity-regulated mechanisms to stimulate growth and progression. Glutamatergic and GABAergic (γ-aminobutyric acid-producing) cortical neuronal activity each drive proliferation of SCLC in the brain through paracrine and synaptic neuron-cancer interactions. SCLC cells form bona fide neuron-to-SCLC synapses and exhibit depolarizing currents with consequent calcium transients in response to neuronal activity; such SCLC cell membrane depolarization is sufficient to promote the growth of intracranial tumours. Together, these findings illustrate that neuronal activity has a crucial role in dictating SCLC pathogenesis.
    DOI:  https://doi.org/10.1038/s41586-025-09492-z
  2. Adv Sci (Weinh). 2025 Sep 09. e06813
    Cancer Neuroscience: Decoding Neural Circuitry in Tumor Evolution for Targeted Therapy.
    Mengyu Yuan, Rongjiao Xi, Yong Kang, Ming-Jie Kuang, Xiaoyuan Ji.
      Recent breakthroughs in tumor biology have redefined the tumor microenvironment as a dynamic ecosystem in which the nervous system has emerged as a pivotal regulator of oncogenesis. In addition to their classical developmental roles, neural‒tumor interactions orchestrate a sophisticated network that drives cancer initiation, stemness maintenance, metabolic reprogramming, and therapeutic evasion. This crosstalk operates through multimodal mechanisms, including paracrine signaling, electrophysiological interactions, and structural innervation guided by axon-derived guidance molecules. Key discoveries reveal that tumors actively recruit and remodel local neurons, hijacking neurodevelopmental pathways to foster invasive growth. Moreover, malignant cells exhibit neuronal-like plasticity, adopting electrophysiological properties that increase survival under therapeutic stress. These findings position neural mimicry as a hallmark of aggressive cancers. The expanding field of cancer neuroscience seeks to unravel the essential signaling factors that drive the complex communication between cancer and the nervous system, utilizing these findings to enhance precision therapies for cancer management. In this Review, we highlight considerable advancements in cancer neuroscience studies, sparking further discussions on various research possibilities and outlining a direction for future investigations. Additionally, we explored promising therapeutic strategies rooted in neural-tumor interactions that could synergize with conventional standard treatments, offering renewed therapeutic vigor for many refractory malignancies.
    Keywords:  cancer neuroscience; cancer therapy; nervous system; neural–tumor interaction; tumor microenvironment
    DOI:  https://doi.org/10.1002/advs.202506813
  3. Cell Rep. 2025 Sep 10. pii: S2211-1247(25)01029-0. [Epub ahead of print]44(9): 116258
    Next-gen tools in cancer neuroscience.
    Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara McErlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair.
      The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.
    Keywords:  CP: Cancer; CP: Neuroscience; cancer neuroscience; chemogenetics; imaging; optogenetics; transcriptomics; viral vectors
    DOI:  https://doi.org/10.1016/j.celrep.2025.116258
  4. Adv Sci (Weinh). 2025 Sep 09. e11726
    Vitamin D Binding Protein, a Ligand of Integrin beta 1, Motivates Both Tumor Cells and Schwann Cells to Promote Perineural Invasion in Pancreatic Ductal Adenocarcinoma.
    Shan Zhang, Luju Jiang, Shuqi Cai, Zheqi Weng, Yuheng Zhu, Zhi-Wei Cai, Hui Li, Qing Li, Li-Peng Hu, Hong-Fei Yao, Rong Hua, Yu Zhao, Dongxue Li, Xiao-Mei Yang, Jun-Feng Zhang, Shu-Heng Jiang.
      Perineural invasion (PNI) is a common pathological characteristic of pancreatic ductal adenocarcinoma (PDAC), closely linked to postoperative recurrence, metastasis, and unfavorable prognosis. Nevertheless, the precise mechanisms that govern PNI in PDAC remain poorly elucidated. Here, group-specific component protein (GC) is identified as one of the most significantly upregulated genes related to PNI, primarily derived from malignant ductal cells compared to other cell types. GC knockdown attenuates PDAC cell invasiveness toward nerves, and this effect operates independently of vitamin D transport. Moreover, GC protein activates Schwann cells by inducing a dedifferentiation program, and enhances the mutual chemoattraction between PDAC cells and Schwann cells. Mechanistically, integrin β1 (ITGB1) serves as the functional receptor for GC protein in both PDAC and Schwann cells. Targeting the ITGB1-FAK signaling cascade proves effective in reducing PNI and Schwann cell activation. In KPC (Pdx-Cre; LSL-KrasG12D+; LSL-Trp53R172H/+) mice and orthotopic xenografts model, GC silencing and ITGB1 blockade both efficiently reduce cancer-nerve interactions and mitigate PDAC progression. Clinically, GC protein, ITGB1, and phosphorylated-FAK are positively associated with the severity of PNI in PDAC cases. Collectively, these data demonstrate that GC protein engages integrin receptor signaling to display distinct functions in cancer cells and Schwann cells, thus enabling PNI.
    Keywords:  VDBP; cancer neuroscience; neural invasion; pancreatic cancer; tumor microenvironment
    DOI:  https://doi.org/10.1002/advs.202511726
  5. Front Oncol. 2025 ;15 1612143
    Identification of key genes associated with perineural invasion in stage II colorectal cancer and their prognostic implications.
    Chen Chang, Bin Zhang, Jingli Chen, Guorong Wang.
       Objective: This study aimed to identify key genes associated with perineural invasion (PNI) in stage II colorectal cancer (CRC) and develop a prognostic nomogram. The goal was to create a model for more precise prognosis assessment and to guide personalized treatment for stage II CRC patients with PNI.
    Methods: Bioinformatic analysis of The Cancer Genome Atlas (TCGA) database was used to identify differentially expressed genes (DEGs) associated with PNI in stage II CRC. Kaplan-Meier and Cox regression analyses identified prognostic genes for overall survival (OS). These genes, along with clinical factors, were integrated into a nomogram. The model's performance was evaluated using calibration curves, receiver operating characteristic (ROC)/area under the curve (AUC) analysis, and decision curve analysis (DCA). Key gene expression in CRC tissues was validated by immunohistochemistry (IHC) and correlated with clinicopathological parameters.
    Results: We identified 33 DEGs associated with stage II CRC and PNI. High expression of CLDN18 and FTCD were independent poor prognostic indicators. A nomogram incorporating these genes and clinical factors accurately predicted 1-, 3-, and 5-year overall survival (OS), with AUC values exceeding 0.7. Calibration curves and DCA confirmed the model's clinical utility. Immunohistochemistry (IHC) revealed that Claudin 18 protein expression was significantly higher in PNI-positive CRC tissues (P < 0.05) and correlated with age and lymphatic invasion (P < 0.05).
    Conclusion: We developed a novel prognostic nomogram for stage II CRC patients with PNI. This model provides a new tool for CRC prognosis, deepens the understanding of PNI pathogenesis, and helps identify therapeutic targets like Claudin 18, whose expression was confirmed as a potential biomarker. This tool can enhance personalized treatment strategies for this high-risk patient population.
    Keywords:  colorectal cancer; differentially expressed genes; nomogram model; perineural invasion; prognostic evaluation
    DOI:  https://doi.org/10.3389/fonc.2025.1612143
  6. J Adv Res. 2025 Sep 04. pii: S2090-1232(25)00668-X. [Epub ahead of print]
    Unraveling the nexus in the neuro-neoplastic progression of colorectal cancer: Potential role of β2-adrenergic receptor (β2-AR).
    Elizabeth Varghese, Samson Mathews Samuel, Slavomir Hornak, Peter Kubatka, Dietrich Büsselberg.
       BACKGROUND: Studies on the interaction of cancer cells with other cells (fibroblasts, endothelial cells, and immune cells) of the tumor microenvironment (TME) have led to the development of many novel targeted therapies. More recently, the notion that neuronal cells of the TME could impact various processes supporting cancer progression has gained momentum. Tumor-associated neurons release neurotransmitters into the TME that, in turn, bind to specific receptors on different target cells, supporting cancer progression. Furthermore, cancer cells secrete nerve growth factors and neurotropic factors that facilitate the growth of nerve fibers that innervate the tumor. In this regard, the beta 2-adrenergic receptors (β2-AR), which respond to neurotropic factors such as catecholamines, are highly expressed in cancer cells, including colorectal cancer (CRC).
    AIM OF REVIEW: Understanding the complexity of the neuronal-cancer axis and identifying targets for molecular therapy is essential. This review focuses on the role of β2-AR in neuro-neoplastic cell signaling during CRC progression and its clinical relevance to diagnosis, prognosis, and treatment.
    KEY SCIENTIFIC CONCEPTS OF REVIEW: The expression of β2-AR on CRC and various other cells of the colorectal TME, along with its responsiveness to agonists or antagonists, is of particular interest since targeting β2-AR and related pathways could curb CRC growth. In the current article, we provide an in-depth review of the possible central role of β2-AR in CRC cancer progression, with special reference to stress-induced activation of the nervous system, catecholamine release, hyperactivation of adrenergic signaling concerning the activation of downstream oncogenic pathways, immuno-modulation, and metastasis. The article also emphasizes the clinical significance of β2-AR expression, its potential as a diagnostic/prognostic biomarker, and the benefits of targeting (by repurposing β-blockers) β2-AR in combination therapies to improve the therapeutic efficacy of current treatment options and overall patient outcomes.
    Keywords:  Beta blockers; Cell signaling; Cellular stress; Colorectal cancer; Nerve-cancer crosstalk; Neuro-neoplastic progression; Physiological stress; β2-adrenergic receptors
    DOI:  https://doi.org/10.1016/j.jare.2025.08.052
This page is being maintained by Thomas Krichel. It was last updated on 2025‒10‒15 at 22:06.