bims-netuvo 2025-10-05 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2025–10–05
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Sensory neuro-tumor crosstalk: Therapeutic opportunities and emerging frontiers in cancer neuroscience.
Nerves, nodes, and neoplasia.
Targeting tumor-associated nerves enhances cancer immunotherapy.
Radiomics analysis using machine learning to predict perineural invasion in pancreatic cancer.
The Neuro-Immune Oncology Axis.
Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors.
Adrenergic signals influence proteomic responses in breast cancer cells.
Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with small cell lung cancer: A dramatic recovery after chemotherapy.

Biochim Biophys Acta Rev Cancer. 2025 Sep 26. pii: S0304-419X(25)00206-9. [Epub ahead of print]1880(6): 189464

Sensory neuro-tumor crosstalk: Therapeutic opportunities and emerging frontiers in cancer neuroscience.

Ying Wang, Zhixin Ye, Ye Yuan, Chuanhao Wang, Gang Chen, Yonghui Zhang.

  Emerging evidence in cancer neuroscience highlights the crucial role of sensory nerves in tumor progression, an aspect of cancer pathobiology previously overlooked. Mechanistically, tumor-associated sensory neurons establish a self-reinforcing oncogenic loop via secreted neurotrophic factors (e.g., NGF/BDNF), which directly promote cancer cell growth, spread, and treatment resistance through Trk activation. Concurrently, tumors rewire their local environment through dysregulated expression of axon guidance molecules, facilitating invasive growth. Importantly, nociceptive signaling activated during perineural invasion not only mediates cancer-related pain but also shapes an immunosuppressive microenvironment through neuropeptide-mediated changes in immune cell function. Current therapeutic strategies targeting tumor-associated nerves focus on: (1) Pharmacological blockade of nerve-tumor communication using small-molecule inhibitors (e.g., Trk inhibitor larotrectinib); (2) Bioelectronic modulation of neural activity via modalities such as transcutaneous electrical nerve stimulation. Notably, preclinical models reveal enhanced efficacy when combining neural modulation with immune checkpoint inhibitors. Technological breakthroughs, including single-cell analysis for precise nerve targeting and advanced drug delivery systems, are improving therapeutic precision. Consequently, understanding the complex interactions between nerves and tumors requires integrated approaches combining cancer biology, neuroimmunology, and systems neuroscience. This conceptual shift not only reshapes our understanding of cancer pathophysiology but also opens new avenues for precision therapies aligned with modern oncology.

Keywords:  Cancer neuroscience; Cancer pain; Nerve remodeling; Neurogenic immunosuppression; Neuromodulation therapy; Sensory innervation

DOI:  https://doi.org/10.1016/j.bbcan.2025.189464
Front Immunol. 2025 ;16 1674174

Nerves, nodes, and neoplasia.

Minjun Wang, Censhan Ran, Quan Liu.

  Tumor immune evasion and incomplete responses to immunotherapy are some of the most significant obstacles in current cancer treatment. Since tumor-draining LNs (tdLNs) are cradles for anti-tumor immunity, and tumor-specific memory cells in tdLNs are the bona fide responders to immune-checkpoint blockade, tdLNs are increasingly valued in oncoimmunology research and cancer treatments. Recent progress has revealed that lymph nodes (LNs) are innervated and regulated by sensory and sympathetic nerve fibers. Because tumor cells, nerves, and immune cells coexist inside tdLNs-sites where anti-tumor immunity is initiated and compromised-it is critical to investigate whether tumor-neuro-immune crosstalk also occurs in these nodes. Although direct evidence in tdLNs is lacking, we synthesize emerging evidence supporting this possibility. We argue that validating this hypothesis will be essential for elucidating immune evasion mechanisms and advancing surgical and immunological strategies against tumors. In this review, we first introduce LN anatomy, highlighting its innervation by sensory and sympathetic fibers. We then examine the neural regulation of immune activities, especially those within LNs and those associated with a tumor context. We further discuss the multifaceted roles of tdLNs in tumor immunology, including orchestration of anti-tumor immunity and local immunosuppression, pre-metastatic LN remodeling, and induction of systemic tumor-specific immune tolerance. Furthermore, we look into tumor-neural interactions from two angles: tumor-induced nerve growth and activation, and neural regulation of tumor progression. Finally, we propose potential tumor-neuro-immune interactions in tdLNs, discuss current perspectives on LN handling in cancer therapy, and discuss clinical implications of the progress summarized in this review.

Keywords:  immunotherapy; lymph node; nociceptor; sympathetic nerve; tumor immunity

DOI:  https://doi.org/10.3389/fimmu.2025.1674174
Neuron. 2025 Oct 01. pii: S0896-6273(25)00671-3. [Epub ahead of print]113(19): 3076-3078

Targeting tumor-associated nerves enhances cancer immunotherapy.

Canhui Cao.

Tumor-associated nerves actively shape tumor immunity. In a recent issue of Nature, Baruch et al.1 show that cancer-induced nerve injury drives T cell exhaustion and undermines PD-1 blockade. Targeting this neuro-immune crosstalk is a promising strategy to enhance cancer immunotherapy.

DOI: https://doi.org/10.1016/j.neuron.2025.09.005
BMC Cancer. 2025 Sep 30. 25(1): 1480

Radiomics analysis using machine learning to predict perineural invasion in pancreatic cancer.

Yuan Sun, Yan Li, Ming Li, Tao Hu, Jiangyu Wang.

   BACKGROUND: Pancreatic cancer is one of the most aggressive and lethal malignancies of the digestive system and is characterized by an extremely low five-year survival rate. The perineural invasion (PNI) status in patients with pancreatic cancer is positively correlated with adverse prognoses, including overall survival and recurrence-free survival. Emerging radiomic methods can reveal subtle variations in tumor structure by analyzing preoperative contrast-enhanced computed tomography (CECT) imaging data. Therefore, we propose the development of a preoperative CECT-based radiomic model to predict the risk of PNI in patients with pancreatic cancer.
PATIENTS AND METHODS: This study enrolled patients with pancreatic malignancies who underwent radical resection. Computerized tools were employed to extract radiomic features from tumor regions of interest (ROIs). The optimal radiomic features associated with PNI were selected to construct a radiomic score (RadScore). The model's reliability was comprehensively evaluated by integrating clinical and follow-up information, with SHapley Additive exPlanations (SHAP)-based visualization to interpret the decision-making processes.
RESULTS: A total of 167 patients with pancreatic malignancies were included. From the CECT images, 851 radiomic features were extracted, 22 of which were identified as most strongly correlated with PNI. These 22 features were evaluated using seven machine learning methods. We ultimately selected the Gaussian naive Bayes model, which demonstrated robust predictive performance in both the training and validation cohorts, and achieved area under the ROC curve (AUC) values of 0.899 and 0.813, respectively. Among the clinical features, maximum tumor diameter, CA-199 level, blood glucose concentration, and lymph node metastasis were found to be independent risk factors for PNI. The integrated model yielded AUCs of 0.945 (training cohort) and 0.881 (validation cohort). Decision curve analysis confirmed the clinical utility of the ensemble model to predict perineural invasion.
CONCLUSION: The combined model integrating clinical and radiomic features exhibited excellent performance in predicting the probability of perineural invasion in patients with pancreatic cancer. This approach has significant potential to optimize therapeutic decision-making and prognostic evaluation in patients with PNI.

Keywords:  Contrast-enhanced computed tomography; Pancreatic cancer; Perineural invasion; Prediction model; Radiomics

DOI:  https://doi.org/10.1186/s12885-025-14806-5
Cancer Lett. 2025 Sep 29. pii: S0304-3835(25)00642-1. [Epub ahead of print] 218070

The Neuro-Immune Oncology Axis.

Fabien Vanden Abeele, Michel Salzet.

  Cancer was long viewed primarily as a genetic disease of uncontrolled cellular proliferation. However, emerging evidence highlights the crucial influence of the tumor microenvironment, particularly the interplay between the nervous and immune systems, in driving cancer progression. Recent discoveries, notably the migration of neural progenitor cells from the central nervous system (CNS) to peripheral tumors, introduce a paradigm wherein neural stem cells actively contribute to tumor initiation and progression. In this framework, CNS-derived neural progenitors infiltrate developing tumors, establish new neural networks, and engage in bidirectional communication with immune cells via neuronal signaling molecules (neurotransmitters, neuropeptides, and even ion channels such as ORAI3 and TRPV1). Here we review the detailed molecular and cellular mechanisms underlying this neuro-immune axis in cancer, emphasizing how neurotransmitter signaling, neuropeptide release, and specialized ion channels mediate cross-talk between nerves, immune cells, and malignant cells. We examine these interactions in the context of specific cancers prostate, breast, lung, and pancreatic to illustrate how neural inputs shape immune evasion and tumor progression in each setting. The clinical relevance of neuro-immune crosstalk is discussed, including evidence that tumor innervation correlates with prognosis and can modulate responses to therapy. Finally, we outline emerging therapeutic strategies targeting neural-immune interactions, such as neuromodulatory drugs and nerve-stimulation interventions, which hold promise for enhancing antitumor immunity. By synthesizing these recent insights, we propose a novel view of cancer as a disease of disrupted neuro-immune communication and highlight opportunities to exploit this axis for improved cancer treatment.

Keywords:  Neuroendocrine Neoplasm; Neuroimmunity; Oncology; cancers; cytokines; ion channels; neuropeptides; neurotransmitters; signaling

DOI:  https://doi.org/10.1016/j.canlet.2025.218070
Mol Cancer Ther. 2025 Oct 02.

Pharmacogenomic synthetic lethal screens reveal hidden vulnerabilities and new therapeutic approaches for treatment of NF1-associated tumors.

Kyle B Williams, Alex T Larsson, Bryant J Keller, Katherine E Chaney, Rory L Williams, Minu M Bhunia, Garrett M Draper, Tyler A Jubenville, Wendy A Hudson, Gunda I Georg, Christopher L Moertel, Nancy Ratner, David A Largaespada.

Neurofibromatosis Type 1 (NF1) is a common cancer predisposition syndrome caused by heterozygous loss of function mutations in the tumor suppressor gene NF1. Individuals with NF1 develop benign tumors of the peripheral nervous system (neurofibromas), originating from the Schwann cell linage after somatic loss of the wild-type NF1 allele, some of which progress further to malignant peripheral nerve sheath tumors (MPNST). There is only one FDA-approved targeted therapy for symptomatic plexiform neurofibromas and none approved for MPNST. The genetic basis of NF1 syndrome makes associated tumors ideal for using synthetic drug sensitivity approaches to uncover therapeutic vulnerabilities. We developed a drug discovery pipeline to identify therapeutics for NF1-related tumors using isogeneic pairs of NF1-proficient and deficient immortalized human Schwann cells. We utilized these in a large-scale high throughput screen (HTS) for drugs that preferentially kill NF1-deficient cells, through which we identified 23 compounds capable of killing NF1-deficient Schwann cells with selectivity. Multiple hits from this screen clustered into classes defined by the method of action. Four clinically interesting drugs from these classes were tested in vivo using both a genetically engineered mouse model of high-grade peripheral nerve sheath tumors and human MPNST xenografts. All drugs tested showed single-agent efficacy in these models as well as significant synergy when used in combination with the MEK inhibitor Selumetinib. This HTS platform yielded novel therapeutically relevant compounds for the treatment of NF1-associated tumors and can serve as a tool to rapidly evaluate new compounds and combinations in the future.

DOI: https://doi.org/10.1158/1535-7163.MCT-24-1053
Front Neurosci. 2025 ;19 1608017

Adrenergic signals influence proteomic responses in breast cancer cells.

Manuel Carrasco, Ole Vidhammer Bjørnstad, Heidrun Vethe, Lars A Akslen.

   Introduction: Breast cancer remains a major health challenge due to its molecular heterogeneity and complex interactions with the tumor microenvironment. Adrenergic signaling, mediated by stress hormones such as noradrenaline, has emerged as a potential regulator of cancer progression, influencing cell proliferation, cell adhesion, migration, and invasion.
Methods: This study investigates the effects of adrenergic modulation on breast cancer spheroids from basal-like (MDA-MB-231, BT549) and luminal-like (T47D, MCF7) cell lines, using 3D culture systems as a more physiologically relevant model compared to traditional 2D monolayer cultures. The 3D spheroid model better recapitulates the structural complexity of tumors, providing insights into cell-cell and cell-matrix interactions that influence signaling pathways and drug responses.
Results: Noradrenaline treatment significantly reduced spheroid size, invasion capacity, and the expression of EMT-related markers and integrins in MDA-MB-231 cells. These effects were partially reversed by propranolol, a non-selective beta-adrenergic receptor antagonist. Luminal-like spheroids, characterized by low ADRB2 abundance, displayed limited responsiveness to adrenergic modulation. Proteomic analysis revealed distinct subtype-specific responses, with basal-like spheroids showing pronounced alterations in pathways related to proliferation, cytoskeletal dynamics, epithelial-mesenchymal transition, and metabolism, whereas luminal-like spheroids exhibited minimal changes.
Discussion: Our findings reveal heterogeneity in adrenergic receptor signaling across basal-like and luminal-like breast cancer cell lines, and also within the basal-like subgroup. This diversity underscores the complexity of adrenergic signaling in breast cancer and highlights the advantages of 3D culture systems. These results provide valuable insights into the subtype-specific patterns of response to adrenergic signaling that contribute to tumor progression and may inform future studies including evaluation of therapeutic strategies.

Keywords:  adrenergic signaling; breast cancer; noradrenaline; propranolol; proteomics

DOI:  https://doi.org/10.3389/fnins.2025.1608017
Intern Med. 2025 Oct 02.

Paraneoplastic anti-N-methyl-D-aspartate receptor encephalitis associated with small cell lung cancer: A dramatic recovery after chemotherapy.

Koichi Yano, Takuto Ishida, Kyoko Yokosuka, Kentaro Sakashita, Masafumi Mizuno.

  Tumor management is the cornerstone of treatment for anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis that is refractory to immunosuppressive therapy. However, little is known about the effectiveness of chemotherapy for malignant tumors in patients with severe neurological conditions. We herein report a 66-year-old male who fell into a coma caused by anti-NMDAR encephalitis associated with small cell lung cancer (SCLC). Corticosteroid pulse therapy failed to improve his neurological condition, but a chemotherapy regimen containing atezolizumab led to rapid improvement in his condition. This case suggests that chemotherapy, including atezolizumab, may provide a rapid therapeutic benefit for anti-NMDAR encephalitis associated with SCLC.

Keywords:  anti-NMDAR encephalitis; atezolizumab; chemotherapy; coma; paraneoplastic; small-cell lung cancer

DOI:  https://doi.org/10.2169/internalmedicine.5586-25