bims-netuvo 2026-03-01 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–03–01
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.
Nervous and immune system crosstalk shapes cancer progression and treatment response.
The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.
MUC15 Loss Promotes Perineural Invasion in Pancreatic Cancer by Activating the IGF1R/STAT3/NGF Pathway.
Perineural Invasion in Radical Prostatectomy Specimens and Its Association with Biochemical Recurrence and Survival in Prostate Cancer: A Systematic Review and Meta-analysis.
Deciphering and Targeting the Schwannoma-Neuron-Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain.
Clinical Outcomes Following Surgical Resection for Patients With Malignant Peripheral Nerve Sheath Tumors.
Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.

Signal Transduct Target Ther. 2026 Feb 23. pii: 66. [Epub ahead of print]11(1):

Cancer neuroscience: signaling pathways and new therapeutic strategies for cancer.

Sihui Zhang, Lin Yuan, Ping Lin, Gen Yang, Xikun Zhou, Jinfu Xu, Min Wu, Yongye Huang.

From a neuroscience perspective, cancer neuroscience has emerged as a subfield of cancer research. Presumable mechanisms underlying cancer-related neuronal activity (termed neurosciences) include the induction and modulation of signaling pathways that govern cell fate determination and emotional responses (anxiety and stress), such as structural molecules (synaptic structures and current transduction) and secretory substances (neurotransmitters, cytokines, hormones and neuropeptides). In the past 3 years, these neuronal activities, which can either promote cancer growth or be hijacked by cancer cells to support tumor survival and invasion, have been widely demonstrated to be closely related to cancer progression. The molecular mechanisms are also being refined. Despite their great promise, translating neuroscientific discoveries into clinically actionable strategies for cancer diagnosis, prognosis, and treatment remains a formidable task. In this comprehensive review, we attempt to provide a full account of the intersection between neuroscience and cancer research. From the perspective of cancer neuroscience, we fully discuss the potential signaling molecules and their regulatory mechanisms, as well as targets and emerging therapeutic strategies that control tumor progression via multiomics approaches. Overall, cancer neuroscience may have unprecedented potential for understanding neuronal functions and cancer development, ultimately offering the significantly improved cancer treatment.

DOI: https://doi.org/10.1038/s41392-025-02364-y
Discov Oncol. 2026 Feb 22.

Nervous and immune system crosstalk shapes cancer progression and treatment response.

Mustafa TArdah, Raghda AliBakr, H Malathi, Vimal Arora, Priya PriyadarshiniNayak, Dilbar Urazbaeva, Mukhayya Djumaniyazova, Sadullayeva Moxinur, Farid KarkonShayan.



Keywords:  Gut-brain axis; Immunotherapy; Neuro-immune-cancer axis; Stress and circadian rhythm; Tumor microenvironment

DOI:  https://doi.org/10.1007/s12672-026-04659-0
Biology (Basel). 2026 Feb 21. pii: 364. [Epub ahead of print]15(4):

The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.

Mohamad Bakir, Alhomam Dabaliz, Mohammed Raddaoui, Hala Fatash, Nourhan Elsaadany, Wael AlKattan, Khalid Said Mohammad.

  Bone metastases represent a major cause of morbidity in advanced cancers, yet the neural regulation of metastatic growth within bone remains largely unexplored. The skeletal system is richly innervated by sensory and sympathetic nerve fibers that influence bone remodeling, hematopoiesis, and immune surveillance. Emerging evidence suggests that disseminated tumor cells exploit these neural circuits to create a growth-permissive microenvironment. Tumor-secreted neurotrophic factors can induce nerve sprouting, while sympathetic activation via β-adrenergic receptors promotes osteoclastogenesis, immunosuppression, and tumor proliferation. Neuropeptides such as substance P and calcitonin gene-related peptide exert dual effects on bone cells and infiltrating immune populations, further shaping the metastatic niche. The interplay between neural signals, osteolytic activity, and immune modulation positions the neuro-bone axis as a critical but underappreciated driver of metastatic progression. In this review, we synthesize current evidence on the anatomy and function of bone innervation, tumor-induced neural remodeling, and neuro-immune-osteoclast interactions. We highlight preclinical and clinical data supporting neuromodulatory strategies, including β-blockers, neurotrophin inhibitors, and targeted nerve ablation, as potential adjuncts to standard bone metastasis therapies. Finally, we identify key knowledge gaps, including the need for spatial and functional mapping of nerve-tumor interfaces and for integrating neuroimaging into bone metastasis detection. By framing the neuro-bone axis as a therapeutic target, we aim to catalyze interdisciplinary research that bridges oncology, neuroscience, and bone biology, with the goal of disrupting neural support for metastatic growth.

Keywords:  bone metastases; neuropeptides; neuro–bone axis; sympathetic nerves; tumor–nerve crosstalk; β-adrenergic signaling

DOI:  https://doi.org/10.3390/biology15040364
Cancer Lett. 2026 Feb 23. pii: S0304-3835(26)00125-4. [Epub ahead of print] 218362

MUC15 Loss Promotes Perineural Invasion in Pancreatic Cancer by Activating the IGF1R/STAT3/NGF Pathway.

Simei Zhang, Tao Qin, Shuai Wu, Zeen Zhu, Wunai Zhang, Yiqun Song, Wanzhen Wei, Ruiqi Cao, Dongmei Liu, Haoyang Zhu, Jianpeng Li, Yangyang Yue, Weikun Qian, Yaomin Zhu, Zheng Wang.

  Perineural invasion (PNI) is a critical yet poorly understood feature that significantly influences the prognosis of pancreatic ductal adenocarcinoma (PDAC), a disease notorious for its dismal survival rates. Although PNI is recognized as a hallmark of pancreatic cancer, the molecular mechanisms underlying this process remain complex and incompletely defined. Recent insights into tumor-nerve interactions have highlighted the role of glycocalyx components, particularly mucin 15 (MUC15), in regulating neural invasion. In this study, we demonstrate that loss of MUC15 promotes PNI by activating the IGF1R/STAT3/NGF signaling axis. Specifically, reduced MUC15 expression weakens its interaction with IGF1R, leading to decreased receptor ubiquitination and increased phosphorylation, which in turn activates STAT3 signaling and drives NGF transcription and secretion. Loss of MUC15 also promotes epithelial-mesenchymal transition (EMT) and alters interactions with the tumor microenvironment, further facilitating neural invasion. Importantly, pharmacologic inhibition of IGF1R reverses these effects, suggesting that restoring MUC15 expression or targeting the IGF1R/STAT3-NGF axis may represent a potential therapeutic strategy to limit PNI in pancreatic cancer. These findings reveal a novel regulatory pathway connecting tumor-intrinsic signaling, EMT, and the neural microenvironment in PDAC progression.

Keywords:  IGF1R/STAT3; Mucin 15; pancreatic cancer; perineural invasion; ubiquitination

DOI:  https://doi.org/10.1016/j.canlet.2026.218362
Eur Urol Open Sci. 2026 Mar;85 99-110

Perineural Invasion in Radical Prostatectomy Specimens and Its Association with Biochemical Recurrence and Survival in Prostate Cancer: A Systematic Review and Meta-analysis.

Jakub Karwacki, Karolina Klasen, Laura Wojdyło, Maciej Kaczorowski, Adam Gurwin, Agnieszka Hałoń, Paweł Rajwa, Fabio Zattoni, Michael Baboudjian, Takafumi Yanagisawa, Patryk Patrzałek, Wojciech Krajewski, Tomasz Szydełko, Bartosz Małkiewicz.

   Background and objective: Perineural invasion (PNI) in prostate cancer (PC) has been linked to adverse oncological outcomes. The objective of this study was to evaluate the association between PNI identified in radical prostatectomy (RP) specimens and survival outcomes.
Methods: A systematic literature search was conducted in December 2024 using PubMed (MEDLINE), Embase, Scopus, and Web of Science Core Collection databases. We included studies reporting on PNI in RP specimens and its association with primary endpoints (biochemical recurrence [BCR] or BCR-free survival) and/or secondary endpoints (cancer-specific survival [CSS], overall survival, recurrence-free survival, disease-free survival [DFS], or metastasis-free survival).
Key findings and limitations: A total of 58 studies met the inclusion criteria. A meta-analysis of 40 studies (27 030 patients) demonstrated that PNI was associated with BCR (pooled hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.28-1.52; p < 0.001). Further analyses showed that PNI was linked to worse CSS (n = 903; pooled HR 2.9, 95% CI 1.1-8.1; p = 0.048). The association with DFS was not statistically significant (n = 1008; pooled HR 1.8, 95% CI 0.7-4.3; p = 0.1). The main limitation is the reliance on predominantly retrospective studies with small samples and high risk of bias.
Conclusions: Our findings indicate that PNI identified in RP specimens is associated with higher risk of BCR, as well as worse CSS, which underscores its relevance as a prognostic factor in PC.
Patient summary: We found that detection of cancer cells around nerves, which is called perineural invasion (PNI), in specimens after surgery to remove the prostate, is linked to a higher chance of worse survival outcomes in prostate cancer. Men with PNI were more likely to experience biochemical recurrence and had worse cancer-specific survival. PNI may help in identifying patients at higher risk after surgery who could benefit from closer follow-up or additional treatment. However, more high-quality studies are needed to confirm its role in guiding long-term care.

Keywords:  Biochemical recurrence; Histopathological examination; Oncological outcomes; Perineural invasion; Prostate cancer; Radical prostatectomy

DOI:  https://doi.org/10.1016/j.euros.2026.01.018
Adv Sci (Weinh). 2026 Feb 27. e15597

Deciphering and Targeting the Schwannoma-Neuron-Macrophage Crosstalk for the Treatment of Schwannomatosis and Associated Pain.

Zhenzhen Yin, Limeng Wu, Yanling Zhang, Yao Sun, Grace Y Lee, Simeng Lu, Xing Gao, John W Chen, Sonu Subudhi, William Ho, Chao Zhu, Jun Ren, Gino B Ferraro, Alona Muzikansky, Anat Stemmer-Rachamimov, Jianren Mao, Scott R Plotkin, Lei Xu.

  Non-NF2 Schwannomatosis (SWN) is a genetic disorder characterized by multiple non-malignant schwannomas growing on the spine and peripheral nerves. Patients with SWN overwhelmingly present with intractable chronic pain. There are no FDA-approved drugs to halt tumor growth or alleviate pain. Research on SWN is hindered by the lack of clinically relevant models. We established patient-derived SWN cell lines from patients with varying pain levels and developed orthotopic patient-derived xenograft models that reproduce patients' pain responses. We further developed a novel dorsal root ganglia (DRG) imaging model for longitudinal intravital imaging of macrophage infiltration into the DRG and sensory neuron pain response. Leveraging these novel models, we found that Schwannomas grown distantly in the peripheral nerve caused an influx of macrophages into the DRG. These macrophages in the DRG caused pain via overproducing IL-6. Treatment with anti-IL-6 antibody reduced pain but had modest efficacy in tumor control. We identified epidermal growth factor receptor (EGFR) signaling as a key driver of schwannoma growth and an escape mechanism from anti-IL6 treatment. Finally, we found that combining IL-6 and EGFR blockade effectively controlled pain and tumor growth simultaneously in SWN models. In summary, we elucidated the cellular and molecular crosstalk between schwannoma (HMGB1), neuron (CCL2), and macrophage (IL-6) in driving pain, and identified the EGF signaling pathway as a driver of SWN tumor progression, thereby uncovering novel therapeutic targets that may improve clinical management of SWN.

Keywords:  EGF‐R inhibitor; Schwannoma‐neuron‐macrophage cross talk; anti‐IL‐6; pain; patient‐derived orthotopic model; schwannomatosis

DOI:  https://doi.org/10.1002/advs.202515597
Neurosurgery. 2026 Feb 27.

Clinical Outcomes Following Surgical Resection for Patients With Malignant Peripheral Nerve Sheath Tumors.

Melanie Alfonzo Horowitz, Jawad M Khalifeh, Xinlan Yang, Oishika Das, Omar Selim, Taha Khalilullah, Abdel-Hameed Al-Mistarehi, Landon Hansen, A Karim Ahmed, Stavriani C Makri, Lindy Zhang, Sahaja Acharya, Jordina Rincon-Torroella, Nicholas Theodore, Sang Lee, John Gross, Carlos G Romo, Christian F Meyer, Christine A Pratilas, Jaishri Blakeley, Allan Belzberg, Daniel Lubelski.

   BACKGROUND AND OBJECTIVES: Malignant peripheral nerve sheath tumors (MPNST) are aggressive soft tissue sarcomas with peripheral nerve differentiation. A wide surgical resection with negative margins is the mainstay of treatment but is not always curative. Here, we present clinical outcomes of patients who underwent surgical resection for MPNST.
METHODS: We identified and collected data on patients who underwent surgical resection for their MPNST at The Johns Hopkins Hospital, from 2010 to 2024. We generated Kaplan-Meier curves and performed univariable and multivariable analyses to determine factors associated with progression-free survival (PFS) and overall survival (OS).
RESULTS: We identified 123 MPNST patients. On univariable analysis, older age (hazard ratio [HR] 1.02), radiation-induced etiology (HR 1.59), spinal tumors (HR 3.27), high-grade pathology (HR 2.6), and postoperative complications (HR 3.07) were each associated with worse OS. Neurofibromatosis type 1 (NF1)-related etiology (HR 0.54), gross total resection (HR 0.48), negative margins (HR 0.58), R0 resection status (HR 0.46), and preoperative ambulatory status (HR 0.26) were each associated with improved OS. The results of the univariable analysis were similar for PFS and for OS and PFS within the NF1-related subgroup. On multivariable analysis, nonextremity MPNST (Spine adjusted hazard ratio [aHR] 3.28, Brachial Plexus aHR 5.51, Head/Neck aHR 6.23), recurrent tumor status (aHR: 2.64), and postoperative complications (aHR 3.27) were independently significantly associated with poor OS.
CONCLUSION: MPNST are aggressive sarcomas that present challenges in diagnosis and treatment. In our series, NF1-related MPNST patients had the highest OS, likely associated with close monitoring for MPNST among the high-risk NF1-population. Nonextremity tumor locations, recurrent tumors, and postoperative complications were associated with inferior OS and PFS. Multi-institutional studies are warranted to investigate the impact of these prognostic factors in a larger, more heterogeneous MPNST patient cohort and examine the utility of surveillance in the neurofibromatosis patient population under a multidisciplinary team.

Keywords:  Malignant peripheral nerve sheath tumor; Neurofibromatosis; Survival

DOI:  https://doi.org/10.1227/neu.0000000000003981
Int J Mol Sci. 2026 Feb 20. pii: 2019. [Epub ahead of print]27(4):

Unraveling the Enigma of Melanoma Brain Metastasis: New Molecular Insights and Therapeutic Directions.

Kayla T O'Toole, Brandon M Roan, Timothy M Hardman, Peyton P Phillips, Evan M VanBrocklin, Gennie L Parkman, Sheri L Holmen.

  Melanoma, a highly aggressive and metastatic cancer, poses significant challenges due to its propensity to spread to distant organs, with brain metastasis representing a particularly devastating complication. This review synthesizes preclinical and clinical evidence on the molecular, cellular, and microenvironmental mechanisms driving melanoma metastasis, emphasizing mechanisms of blood-brain barrier traversal, tumor-stroma co-option, and brain-specific genomic and transcriptional programs. We summarize advances in therapeutic strategies to combat melanoma brain metastasis including novel small molecules, immunotherapies, and combination approaches tailored for brain metastases. The review also highlights the immunological landscape of the brain, translational models, and multidisciplinary clinical management strategies. Finally, we identify critical research gaps, including the need for brain metastasis-specific clinical trials, AI-driven predictive models, and preventive strategies, to guide future efforts in improving outcomes for patients with melanoma brain metastasis.

Keywords:  BRAF; NRAS; PI3K/AKT; brain metastases; brain microenvironment; immune checkpoint inhibitors; melanoma; preclinical models; therapeutic resistance

DOI:  https://doi.org/10.3390/ijms27042019