bims-netuvo 2026-06-21 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–06–21
fourteen papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Context dependency in cancer neuroscience.
Neuron-tumor crosstalk in cancer: molecular mechanisms and translational advances.
Cancer neuroscience in cholangiocarcinoma: from perineural invasion to neuroimmune control.
Neurobiology of cancer: Unraveling the roles of the nervous system in tumor initiation, progression, and therapeutic.
Perineural invasion in gastrointestinal malignancies: From neurotrophic signaling to targetable tumor-microenvironment crosstalk.
Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.
Expression of the Galanin system in the human pancreas, pancreatitis, and pancreatic cancer: Association with nodal involvement and perineural invasion.
Survival and prognosis of neurofibromatosis type 1-associated malignant peripheral nerve sheath tumours: a systematic review and meta-analysis.
Lymphovascular and Perineural Invasion Guides Adjuvant Therapy after Neoadjuvant Chemoimmunotherapy in Esophageal Squamous Cell Carcinoma.
Neuron-targeting piezoelectric microneedles disrupt pro-tumorigenic neuron-immune crosstalk and restore anti-tumor immunity in melanoma.
Unveiling the cognitive fog in lung cancer patients: non-invasive exploration of blood-brain barrier disruption and brain structural changes.
Cell type-specific pharmacological modulation of the neuro-immune axis: the role of ADRB2 signaling in reshaping the tumor ecosystem.
Patterns of central nervous system disease and molecular landscape in epidermal growth factor receptor exon 20 insertion mutated non-small cell carcinoma.
Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.

Cancer Cell. 2026 Jun 18. pii: S1535-6108(26)00261-8. [Epub ahead of print]

Context dependency in cancer neuroscience.

Alexander Birbrair, David J Simon, Sebastien Talbot, Shengtao Zhou.

Neural signaling shapes tumor progression, but it is not intrinsically tumor-promoting or tumor-restrictive. We argue that neural directionality is context-dependent and governed by tumor kinetics, tissue architecture, neural state, receptor and target-cell topology, immune-host biology, and treatment history. We propose a mechanistically interpretable and clinically actionable reporting framework for precision neuromodulatory oncology.

DOI: https://doi.org/10.1016/j.ccell.2026.05.016
Mol Cancer. 2026 Jun 19.

Neuron-tumor crosstalk in cancer: molecular mechanisms and translational advances.

Boqun Jia, Lingyun Zhao, Muhan Tang, Nanbin Xie, Yunqian Huang, Xiaoxia Liang, Guanhu Yang, Qibiao Wu, Zhiguang Sun, Hiu Yee Kwan, Hao Sun, Keyang Xu.

  Tumor neuron hijack is a malignant adaptive program whereby tumor cells recruit, physically engage and functionally reprogram the peripheral and central nervous system within the local microenvironment and host macroenvironment; this process not only exploits neuro-immune regulatory machineries, neural endocrine signaling, and nutrient supply for sustaining tumor growth, invasion, metastasis, immune escape and treatment resistance, but also closely involves the induction and amplification of cancer-associated pain, a common and debilitating manifestation of the host's pathological response to tumor-neural crosstalk, which further perturbs the host macroenvironment and facilitates tumor progression. Neoplastic cells employ context-dependent strategies: central nervous system tumors (e.g., gliomas) integrate into existing neuronal circuits via synaptogenesis and metabolic coupling, while peripheral solid tumors induce de novo innervation via neurotrophic factors, axon guidance cues regulating angiogenesis, and perineural invasion. Sympathetic, parasympathetic, and sensory nerves modulate tumor behavior via neurotransmitters or neuropeptides, with autonomic nerves also regulating endocrine glands to reprogram tumor metabolism. Pivotal to this regulation is the tripartite crosstalk among nerves, immune cells, and tumor cells, which establishes an immunosuppressive tumor microenvironment and drives progression from immune equilibrium to escape. These mechanisms have spurred therapeutic avenues such as neurotrophic agent repurposing, synaptic blockade, and neural-signal reprogramming, particularly in combination with immunotherapy, with promising preclinical and translational potential for precision oncology and cancer pain management.

Keywords:  Metabolic plasticity; Neuroendocrine axis; Neuropathic pain; Tumor immune microenvironment; Tumor neuron hijack; Tumor-neuro crosstalk

DOI:  https://doi.org/10.1186/s12943-026-02715-5
Gut. 2026 Jun 17. pii: gutjnl-2026-338969. [Epub ahead of print]

Cancer neuroscience in cholangiocarcinoma: from perineural invasion to neuroimmune control.

Maria Backhaus, Lorenzo Mainardi, Chiara Raggi, Kai Markus Schneider.



Keywords:  CANCER; CHOLANGIOCARCINOMA; IMMUNOLOGY; NEUROIMMUNOLOGY

DOI:  https://doi.org/10.1136/gutjnl-2026-338969
Chin Med J (Engl). 2026 Jun 16.

Neurobiology of cancer: Unraveling the roles of the nervous system in tumor initiation, progression, and therapeutic.

Liang Zhou, Xiang Luo, Tianjie Bao, Hongbao Sun, Chengqi He, Yonghong Yang, Yong Xia.

   ABSTRACT: Accumulating evidence highlights a complex interplay between the nervous system and cancer; the nervous system has a significant influence on tumor progression. This review explores the burgeoning field of neuro-oncology, focusing on the nervous system's role in tumor initiation, growth, invasion, metastasis, and treatment response. In most cases, the nervous system interacts with the tumor microenvironment (TME) through its extensive and highly intricate network at both the local and systemic levels, thereby promoting malignant behaviors such as tumor growth, invasion, and metastasis. Conversely, in certain tumor types, neural-tumor interactions may suppress tumor progression. This bidirectional regulatory phenomenon highlights the complex and diverse role of the nervous system in tumor development. Within the TME, the nervous system influences tumor progression through multiple mechanisms, including synaptic connections, paracrine signaling, and immune regulation. Studies show that in brain tumors, neurons and glial cells can promote tumor growth and treatment resistance through neurotransmitter release, synaptic signaling, and inflammatory modulation, whereas in peripheral tumors, autonomic and sensory nerve activity also regulates tumor progression. Understanding these interactions enhances our comprehension of tumor biology and enables the development of innovative therapeutic strategies targeting neuro-cancer interfaces. This interdisciplinary approach, integrating neuroscience, immunology, and oncology, provides insights into cancer-nervous system dynamics, and holds promising potential to advance the development of effective anticancer therapies.

Keywords:  Cancer neuroscience; Cancer treatment; Neuro-oncology; Neuro–immune interaction; Tumor innervation; Tumor microenvironment

DOI:  https://doi.org/10.1097/CM9.0000000000004144
Biochim Biophys Acta Rev Cancer. 2026 Jun 16. pii: S0304-419X(26)00110-1. [Epub ahead of print]1881(4): 189638

Perineural invasion in gastrointestinal malignancies: From neurotrophic signaling to targetable tumor-microenvironment crosstalk.

Qi Li, Jingli Xu, Can Hu, Zhiyuan Xu.

  Perineural invasion (PNI) is increasingly recognized as a distinct metastatic route and a hallmark of aggressive behavior in gastrointestinal (GI) malignancies. This review synthesizes current evidence on the epidemiology, pathobiology, and clinical translation of PNI in digestive system tumors. We first summarize the incidence and prognostic impact of PNI across major GI cancer subtypes. We then delineate the multilayered molecular network that orchestrates PNI. Particular emphasis is placed on the tumor microenvironment as an active driver of PNI. Clinically, we discuss how tumor-nerve crosstalk underlies cancer-induced neuroinflammation and pain, and outline emerging tools and candidate biomarkers for PNI detection. Finally, we review potential therapeutic strategies aimed at disrupting the tumor-nerve axis. A deeper, spatially resolved understanding of the tumor-nerve interface is expected to enable rational biomarker development and dual-function interventions that simultaneously alleviate pain and restrain PNI -driven progression in GI cancers.

Keywords:  Digestive system tumors; Neurotrophic factors; Perineural invasion; Schwann cells; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.bbcan.2026.189638
Cell Commun Signal. 2026 Jun 15.

Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.

Xuanyin Ding, Hele Liu, Weiran Zhang, Jie Shen, Yuting Zhang, Danni Zhao, Minjie Guo, Xiao Yuan, Xu Wang, Dan Feng.

  Recent studies highlight the multifaceted roles of neurotransmitters in tumor immunomodulation, offering novel avenues for increasing therapeutic efficacy. These signaling molecules are classified into cholinergic agents, monoamines, amino acids, and peptides and regulate tumorigenesis, metastasis, and immune evasion via autocrine/paracrine pathways and receptor-mediated interactions. Notably, neurotransmitters influence tumor cell proliferation, apoptosis, and immune cell activity by modulating intracellular signaling cascades through posttranslational modifications (serotonylation and dopaminylation). Emerging evidence highlights their dual roles: serotonin enhances glycolysis in CD8+ T cells to potentiate antitumor responses, while γ-aminobutyric acid accumulates in tumors to promote immune escape. Pharmacological interventions targeting neurotransmitter synthesis, release, or receptor signaling, such as combining antagonists with immune checkpoint inhibitors, result in improved clinical outcomes. Additionally, neurotransmitter-driven tumor vaccines represent a promising frontier. This review synthesizes mechanistic insights into the neurotransmitter-mediated regulation of the tumor microenvironment and proposes innovative strategies to optimize immunotherapy by exploiting neuromodulatory pathways. These findings provide a translational framework for developing precision therapies that integrate neuroimmune crosstalk in oncology.

Keywords:  Immunotherapy; Neuroimmune crosstalk; Neurotransmitters; Posttranslational modifications; Receptor signaling; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12964-026-02998-7
Neuropeptides. 2026 Jun 05. pii: S0143-4179(26)00051-X. [Epub ahead of print]118 102635

Expression of the Galanin system in the human pancreas, pancreatitis, and pancreatic cancer: Association with nodal involvement and perineural invasion.

Sara Huber, Julia Gering, Stefanie Gaisbauer, Theo Kraus, René G Feichtinger, Karl Sotlar, Barbara Kofler, Martin Varga.

  Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies, with a five-year survival rate of 6%, yet the underlying causes remain poorly understood. The neuropeptide galanin (GAL) and its three receptors (GAL1-3-R) are known to modulate tumor biology. This study characterizes the expression patterns of the GAL system in healthy and diseased pancreas to evaluate its potential as a biomarker for disease progression. Immunohistochemical staining for GAL and GAL1-3-R was performed on tissue samples from healthy controls (n = 10), pancreatitis (n = 10), and PDAC (n = 34). Immunoreactive scores were quantified across histological compartments and were correlated with TNM stage, perineural invasion, and Union for International Cancer Control classification. GAL was widely expressed, with significant upregulation in lobular ducts and nerve bundles of PDAC compared to controls. Intra-neural GAL expression in PDAC positively correlated with advanced nodal stages and perineural invasion. In pancreatitis, GAL1-R expression was selectively increased in lobular ducts. Although GAL2-R expression peaked in endocrine cells, intra-neural GAL2-R was significantly downregulated in PDAC compared to healthy tissue, with further decreases in advanced stages. GAL3-R was predominantly localized to ducts and acini, showing higher expression in PDAC endocrine compartments than in pancreatitis or healthy tissue. Our findings demonstrate significant remodeling of the galaninergic system during pancreatic inflammation and carcinogenesis. Stage-dependent intra-neural GAL increases correlate with nodal involvement and perineural invasion, suggesting its potential as a prognostic biomarker for tumor aggressiveness. Progressive intra-neural GAL2-R loss in PDAC may limit receptor-agonist therapy efficacy, necessitating receptor-status screening for personalized patient stratification in future clinical applications.

Keywords:  Galanin; Galanin receptors; Neuropeptides; Pancreas; Pancreatic cancer; Pancreatitis

DOI:  https://doi.org/10.1016/j.npep.2026.102635
Orphanet J Rare Dis. 2026 Jun 17.

Survival and prognosis of neurofibromatosis type 1-associated malignant peripheral nerve sheath tumours: a systematic review and meta-analysis.

Mette Møller Handrup, Ninna Aggerholm-Pedersen, Stine Bogetofte Thomasen, Emma Hyldgaard Olesen, Cecilie Ejerskov.

   BACKGROUND: Malignant peripheral nerve sheath tumour (MPNST) is a rare, aggressive sarcoma with high mortality. MPNST can develop sporadically, after radiation therapy or in association with neurofibromatosis type 1 (NF1). The treatment is challenging especially if surgical removal is not possible. NF1 is an autosomal-dominant genetic disorder most often caused by a germline pathogenic variant in the NF1 gene and in rare cases a deletion of the NF1 gene. Patients with NF1 have a higher risk of developing several different cancers, of which MPNST is one of the most frequent. MPNST in individuals with NF1 often presents with large MPNST which are often not accessible for surgery. Several studies have shown that patients with NF1-associated MPNST (nfMPNST) have an overall inferior survival than those with sporadic MPNST (sMPNST). Despite this, NF1 status alone may not be a causative factor for poor prognosis, which might rather be due to the incidence of larger tumours, which are more challenging to resect in toto.
METHODS AND RESULTS: A systematic research protocol was made using the PRISMA-P model and the review question and inclusion and exclusion criteria were defined using the PICO model. The study characteristics defined by PICO include patients with NF1 as the population of interest. The development of MPNST was considered as the intervention, patients with sMPNST were chosen for comparison and the primary outcome of interest was survival. The literature search was performed on 12 October 2024 and 4,394 studies were eligible for screening, of which 36 studies were included in this study. Meta-analysis of eight studies found NF1 status to be a risk factor for the survival of MPNST. The reported survival rates varied between studies, but the 5-year overall survival (OS) remained poor in general, Awith 15 studies showing a significantly inferior survival for nfMPNST. Only four studies have a worse survival for sMPNST, but none with a significant difference.
CONCLUSION: The findings in this systematic review and meta-analysis of 36 studies indicates that patients with nfMPNST have a worse survival compared to sMPNST.

Keywords:  Neurofibromatosis type 1; Neurofibrosarcoma; Prognosis; Survival rate

DOI:  https://doi.org/10.1186/s13023-026-04460-w
Oncologist. 2026 Jun 13. pii: oyag234. [Epub ahead of print]

Lymphovascular and Perineural Invasion Guides Adjuvant Therapy after Neoadjuvant Chemoimmunotherapy in Esophageal Squamous Cell Carcinoma.

Yizhou Huang, Maohui Chen, Zhenyuan Yang, Bingqiang Cai, Yongcong Zhang, Shuliang Zhang, Taidui Zeng, Jun Yu, Chun Chen, Bin Zheng.

   BACKGROUND: Lymphovascular (LVI) and perineural invasion (PNI) are adverse pathological features in esophageal squamous cell carcinoma (ESCC). We evaluated the prognostic significance of combined LVI/PNI (LNI) after neoadjuvant chemoimmunotherapy (nCIT) and the potential benefit of adjuvant therapy.
METHODS: We retrospectively analyzed 473 ESCC patients undergoing nCIT followed by curative resection. LNI status was assessed in resected specimens. Survival outcomes were compared between LNI-positive and -negative patients using propensity score matching and multivariable Cox models. External validation was performed using an independent patient-level dataset.
RESULTS: LNI was present in 21% of patients. LNI-positive patients had worse 3-year OS (49.8% vs 76.4%) and DFS (41.7% vs 69.3%), which remained significant after matching. LNI independently predicted inferior OS (HR 1.52, P = 0.022) and DFS (HR 1.40, P = 0.045). Recurrence occurred more frequently in LNI-positive patients (39.4% vs 19.8%, P < 0.001), predominantly locoregional. Among LNI-positive patients, adjuvant therapy improved 3-year OS (56.8% vs 32.4%) and DFS (49.7% vs 20.7%; adjusted HR 0.43, P = 0.002). External validation confirmed these findings, with independent prognostic impact of LNI and benefit from adjuvant therapy.
CONCLUSIONS: LNI after nCIT is an independent adverse prognostic factor in ESCC. Patients with these high-risk pathological features have markedly worse outcomes but appear to derive significant benefit from adjuvant therapy, supporting its incorporation into postoperative management.

Keywords:  Esophageal squamous cell carcinoma; Lymphovascular invasion; adjuvant therapy; neoadjuvant chemoimmunotherapy; perineural invasion

DOI:  https://doi.org/10.1093/oncolo/oyag234
Nat Commun. 2026 Jun 19.

Neuron-targeting piezoelectric microneedles disrupt pro-tumorigenic neuron-immune crosstalk and restore anti-tumor immunity in melanoma.

Anjun Song, Yanjie Zhang, Yanjun Ji, Heying Yuan, Jinsong Ren, Xiaogang Qu.

Neuroimmunology has garnered significant attention due to its role in immune regulation, particularly in cancer, where infiltrating neurons can influence antigen presentation, T-cell activation, and cancer metastasis, ultimately leading to an inadequate immune response. Here, we integrate manganese-doped titanium-based metal-organic framework (MOF) piezoelectric materials (MT), coated with neuron-derived membranes from dorsal root ganglia, into microneedles (MN) to create a piezoelectric microneedle (MT MN) patch designed to disrupt neuron-immune crosstalk in melanoma. A single administration of MT via microneedle patch stably deposits the MT at the melanoma site in female mice to accelerate the nociceptor neurons targeting. Upon moderate ultrasound stimulation, the MT facilitates the internalization of TRPV1 and activates the cGAS-STING pathway, resulting in the reduction of Ca2+ influx in nociceptor neurons. This ultimately limits the production of calcitonin gene-related peptide (CGRP) and substance P (SP). Consequently, to rescue the tumor immune microenvironment damaged by infiltrated neurons, MT MN is utilized to inhibit the growth and infiltration of nociceptor neurons, highlighting a promising manner for interfering neuron-immune crosstalk in melanoma to enhance cancer immunotherapy.

DOI: https://doi.org/10.1038/s41467-026-74550-7
Ann Med. 2026 Dec;58(1): 2662776

Unveiling the cognitive fog in lung cancer patients: non-invasive exploration of blood-brain barrier disruption and brain structural changes.

Da-Fu Zhang, Huan Ma, Zhi-Ping Zhang, Jing Ai, Wen-Ting Cao, Zhen-Hui Li.

   BACKGROUND: This study investigates the correlation between blood-brain barrier (BBB) damage and cognitive impairment in patients suffering from untreated lung cancer. The study aims to understand the impact of BBB permeability on cognitive function and brain structure in this patient population.
PATIENTS AND METHODS: This study included 104 lung cancer patients and 40 healthy individuals as controls. The permeability of the blood-brain barrier was evaluated using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The study analyzed the correlation between BBB permeability and both brain structure and cognitive function to determine the extent of BBB damage's influence on cognitive impairment.
RESULTS: The study revealed a significant increase in BBB permeability among lung cancer patients, particularly in those experiencing cognitive impairment. Those with cognitive impairment exhibited a substantial decrease in cortical volume across several brain regions. Notably, the Ktrans value in the right superior parietal cortex was significantly elevated in the cognitive impairment group compared to both the non-cognitive impairment group and the healthy control group.
CONCLUSION(S): The findings indicate a strong association between BBB damage and cognitive impairment in lung cancer patients. DCE-MRI has shown promise as an effective diagnostic tool for assessing BBB damage in the context of lung cancer treatment. This research contributes novel insights into the pathophysiological mechanisms underlying cognitive impairment in lung cancer patients and provides valuable information for the development of personalized therapeutic strategies.

Keywords:  Blood–brain barrier; brain structure; cognitive; dynamic contrast-enhanced MRI; lung cancer

DOI:  https://doi.org/10.1080/07853890.2026.2662776
Front Pharmacol. 2026 ;17 1848277

Cell type-specific pharmacological modulation of the neuro-immune axis: the role of ADRB2 signaling in reshaping the tumor ecosystem.

Wenjun Meng, Mengting Li, Ruoyu Ren, Xiaoli Mu, Bin Hou, Qing Li.

  Adrenergic signaling through β2-adrenergic receptor (ADRB2) is a conserved neuro-immune axis that modulates tumor biology at multiple levels: tumor cells, stromal compartments (CAF, endothelium), myeloid populations (MDSC/TAM), and lymphocytes (CD4+/CD8+). Activation of ADRB2 by stress-related catecholamines (norepinephrine/epinephrine) promotes angiogenesis, pro-metastatic programs and immunosuppression; conversely, ADRB2 blockade in preclinical models reprograms myeloid cells, potentiates T cell-mediated antitumor immunity and synergizes with immune checkpoint blockade in defined contexts. Clinical and epidemiologic data remained heterogeneous, but other small randomized and retrospective studies suggested that short-term pharmacologic suppression of adrenergic signaling (often combined with COX-2 inhibition) can favorably affect biomarkers and, in pilot trials, disease-free survival. This review summarized cell type-specific mechanisms linking ADRB2 to tumor ecosystem remodeling, compared pharmacological strategies for selective and cell-directed ADRB2 modulation, and outlined translational priorities and trial designs to move ADRB2-targeted approaches into practice.

Keywords:  ADRB2; cell type-specific targeting; immune modulation; neuro-immune axis; tumor microenvironment; β-adrenergic signaling; β-blocker

DOI:  https://doi.org/10.3389/fphar.2026.1848277
Transl Lung Cancer Res. 2026 May 31. 15(5): 140

Patterns of central nervous system disease and molecular landscape in epidermal growth factor receptor exon 20 insertion mutated non-small cell carcinoma.

Amanda Reyes, Isa Mambetsariev, Jeremy Fricke, Jonathan R Young, Bihong T Chen, Arya Amini, Colton Ladbury, Javier Arias-Romero, Danny Nguyen, Evan Pisick, Vicki Doctor, Bradford Tan, Michelle Afkhami, Waasil Kareem, Xiaochen Li, Ravi Salgia.

   Background: Epidermal growth factor receptor exon 20 insertion mutations (EGFR ins20) constitute a distinct entity among EGFR mutations. Therefore, we aimed to characterize patterns of central nervous system (CNS) metastasis and molecular co-mutations in relation to survival in this population.
Methods: Retrospective analysis of 80 patients with non-small cell lung cancer and EGFR ins20 mutations seen from 2014-2024 at a large institution and network sites to characterize patterns of metastasis and progression. Clinical outcomes were analyzed with overall survival (OS). Magnetic resonance imaging was used to assess central nervous system disease location and progression.
Results: About 36.25% of the patients had progression in central nervous system with 7.5 % of patients having leptomeningeal disease. Patients with CNS progression had a similar median OS of 45.3 months (31.6-78.5 months) compared to patients without progression of 47.8 months [36.8, not estimated (NE)] with a hazard ratio of 1.21 [95% confidence interval (CI): 0.66-2.23, P=0.54]. Co-TP53 mutation was associated with lower median OS of 31.6 months (20.4-NE) compared to 47.8 months (42.8-72.3) in TP53 wild type; hazard ratio 1.79 (95% CI: 0.89-3.60, P=0.11).
Conclusions: While progression in the central nervous system did not impact clinical outcomes in this patient population, the high rate of disease in the central nervous system does warrant consideration and tailoring treatment with central nervous system penetration. This subgroup continues to behave as a distinct population and as such requires unique treatment and treatment strategies.

Keywords:  Epidermal growth factor receptor exon 20 insertion mutations (EGFR ins20); central nervous system (CNS); co-mutations; leptomeningeal

DOI:  https://doi.org/10.21037/tlcr-2026-1-0104
Cell Metab. 2026 Jun 19. pii: S1550-4131(26)00244-5. [Epub ahead of print]

Cancer cells co-opt nociceptive nerves to thrive in nutrient-poor environments and upon nutrient-starvation therapies.

Yu Zhang, Chengzhong Lin, Zheqi Liu, Yiting Sun, Mingtao Chen, Yibo Guo, Wei Liu, Chenping Zhang, Wantao Chen, Jian Sun, Ronghui Xia, Yuhua Hu, Xi Yang, Jiang Li, Zhiyuan Zhang, Wei Cao, Shuyang Sun, Xu Wang, Tong Ji.

DOI: https://doi.org/10.1016/j.cmet.2026.06.018