bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2026–06–07
nine papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Disarming the "Neural Hijack": Repurposing neuroactive drugs for cancer therapy.
  2. Nerve-proximal tertiary lymphoid structures predict chemotherapy sensitivity in pancreatic cancer.
  3. A multivariate IVIM-DWI-based model for preoperative prediction of perineural invasion status in rectal cancer: a feasibility study.
  4. Pain management in pancreatic cancer: time to change our strategy!
  5. Multidetector computed tomography detection of perineural infiltration around the superior mesenteric artery in intrahepatic cholangiocarcinoma: A case report.
  6. Patient survival outcomes in brain metastases of pancreatic ductal adenocarcinoma: A comprehensive analysis.
  7. Brain Metastases in Pediatric Extracranial Solid Tumors: A 20-Year Experience in Challenging a Rare Diagnosis.
  8. Depression as a potential early indicator of pancreatic cancer: a systematic review of prevalence, mechanisms, and temporal associations.
  9. Mammary tumors-derived exosomes induce striatal NF-κB signaling, microglial reactivity, and anxiety/depression-like behaviors.
  1. Pharmacol Ther. 2026 Jun 03. pii: S0163-7258(26)00078-1. [Epub ahead of print] 109051
    Disarming the "Neural Hijack": Repurposing neuroactive drugs for cancer therapy.
    Ming-Zhu Jin, Hao-Ran Dang, Wei-Lin Jin.
      The emerging field of cancer neuroscience has fundamentally reshaped our understanding of malignancy, revealing tumors as complex ecosystems deeply integrated with and actively shaped by the nervous system. Malignancies recruit, reprogram, and exploit neural components, a phenomenon we conceptualize as "neural hijack" to fuel growth, metastasis, immunosuppression, and therapy resistance. Concurrently, drug repurposing, leveraging the established safety profiles of approved neuroactive agents, has emerged as a powerful strategy to therapeutically dismantle this tumor-neural axis. This review synthesizes the neural hijack paradigm, detailing how cancers co-opt neuropeptide, neurotransmitter, and synaptic signaling pathways. We provide a comprehensive evaluation of repurposed neuroactive drugs, including β-blockers, CGRP antagonists, NK1R antagonists, SSRIs, and anti-epileptics, framing their mechanisms within the disruption of specific hijacking nodes. We further propose "neural signatures", composite biomarkers integrating innervation density, receptor profiles, and neuro-immune contexture as critical tools for precision patient stratification. Finally, we discuss translational challenges and innovative solutions, charting a roadmap toward "neural disconnection", the therapeutic severing of the tumor's neural lifeline, as an emerging pillar of cancer therapy.
    Keywords:  Cancer Neuroscience; Drug Repurposing; Neural Hijack; Neuro-Immune Axis; Translational Oncology; Tumor Innervation; Tumor Microenvironment
    DOI:  https://doi.org/10.1016/j.pharmthera.2026.109051
  2. Cell Rep. 2026 Jun 04. pii: S2211-1247(26)00574-7. [Epub ahead of print]45(6): 117496
    Nerve-proximal tertiary lymphoid structures predict chemotherapy sensitivity in pancreatic cancer.
    Shuqi Cai, Min-Wei Yang, Luju Jiang, Zheqi Weng, Xin Wang, Xueshiyu Ma, Yan-Miao Huo, Wei Liu, Shan Zhang, Shu-Heng Jiang.
      The complex interplay between nerves, immunity, and tumor progression remains poorly understood, particularly in the context of chemotherapy. Here, we investigated how neural remodeling influences tertiary lymphoid structures (TLSs) and clinical outcomes following neoadjuvant chemotherapy (NAT) in pancreatic ductal adenocarcinoma (PDAC). Using tissue samples from 86 treatment-naïve and 49 NAT-treated patients with PDAC, we demonstrated that chemotherapy significantly increases both nerve density (ND) and TLS abundance. Notably, nerve-proximal TLSs (N-TLSs) displayed more mature phenotypes and correlated positively with tumor regression. Spatial transcriptomics of nerve regions showed chemotherapy-induced transcriptional reprogramming of Schwann cells, marked by altered myelination programs and elevated pro-inflammatory signaling. The Schwann cell state shift coincides with TLS accumulation, maturation, and enhanced peri-neural immune infiltration. Collectively, our study indicates a spatially organized neuro-immune axis linking neural remodeling to TLS abundance and maturation after chemotherapy and nominates N-TLS abundance as a potential histological biomarker of treatment response in resected PDAC.
    Keywords:  CP: cancer; CP: neuroscience; antitumor immunity; cancer neuroscience; nerve dependence; nerve-cancer interactions; neuroimmunology; pancreatic cancer; perineural invasion; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.celrep.2026.117496
  3. MAGMA. 2026 Jun 06.
    A multivariate IVIM-DWI-based model for preoperative prediction of perineural invasion status in rectal cancer: a feasibility study.
    Yantong Sun, Yi Wang, Hongyu Zhao, Longxia Xu, Dmytro Pylypenko, Yafei Liu, Haojie Sun, Gesheng Song, Aiyin Li.
       OBJECTIVE: To evaluate intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) for preoperative diagnosis of perineural invasion (PNI) in rectal cancer (RC).
    MATERIALS AND METHODS: A total of 148 patients with pathology-confirmed RC (PNI+, n = 72; PNI-, n = 76) were enrolled. Parameters from mono-exponential (ADC), bi-exponential (D, D*, f), and stretched-exponential (DDC, α) IVIM models were analyzed. Univariate and multivariate logistic regression analyses were used to construct diagnostic models. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. The DeLong test was used to compare the AUC of the models. Internal validation was employed to assess model performance. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI), along with calibration metrics and decision curve analysis, were used to further evaluate model performance. P-value < 0.05 was considered statistically significant.
    RESULTS: ADC, D, f, and DDC differed significantly between groups. Multivariate analysis identified ADC and D as independent PNI predictors. The D value yielded the highest AUC (0.84), while ADC showed the highest sensitivity (81.94%). A combined model (ADC + D) achieved an AUC of 0.85, sensitivity of 86.10%, specificity of 73.70%, and accuracy of 77.00%. The fivefold internal validation mean AUC was 0.84 ± 0.04. No significant AUC differences were found among parameters or models (DeLong test, P > 0.05). Further analyses revealed that the combined model provided significant improvements over the ADC model in individual risk reclassification (continuous NRI = 0.65, 95% CI 0.33-0.95), overall predictive accuracy (IDI = 0.07, 95% CI excluding 0), and calibration (Brier score: 0.16 vs. 0.17; MAE: 0.01 vs. 0.04; MSE: 2.3×10⁻⁴ vs. 1.91×10⁻³). Decision curve analysis demonstrated consistently higher net benefit for the combined model across threshold probabilities of 0-0.50.
    CONCLUSION: IVIM-DWI demonstrates potential value for the preoperative assessment of PNI status in rectal cancer and may facilitate individualized treatment planning.
    Keywords:  Diffusion magnetic resonance imaging; Magnetic resonance imaging; Nomogram; Perineural invasion
    DOI:  https://doi.org/10.1007/s10334-026-01374-3
  4. Curr Opin Oncol. 2026 Jul 01. 38(4): 359-363
    Pain management in pancreatic cancer: time to change our strategy!
    Daniel Blero, Alain Hendlisz.
      Pain affects 70-80% of patients with pancreatic adenocarcinoma and remains inadequately controlled in more than half of cases. Beyond its impact on quality of life, pain is now recognized as an independent prognostic factor, reflecting the unique neurobiological features of this malignancy. Perineural invasion drives a bidirectional dialogue between cancer cells and the peripheral nervous system, in which neurotrophic factors, neuropeptides, and immune mediators fuel both nociception and tumour progression. Current pain management relies on the WHO analgesic ladder supplemented by adjuvant agents (gabapentinoids, duloxetine, corticosteroids) and interventional procedures including celiac plexus neurolysis, intrathecal opioid delivery, and palliative radiotherapy. Recent advances, notably celiac plexus radiosurgery and evidence favouring early neurolysis, challenge the prevailing reactive approach. This review examines the pathophysiology of pancreatic cancer pain, critically appraises available treatments, identifies gaps in current evidence, and argues for a proactive, multimodal strategy initiated at diagnosis rather than reserved for refractory disease.
    Keywords:  celiac plexus; pain management; palliative care; pancreatic neoplasms; tumour microenvironment
    DOI:  https://doi.org/10.1097/CCO.0000000000001251
  5. Oncol Lett. 2026 Jul;32(1): 303
    Multidetector computed tomography detection of perineural infiltration around the superior mesenteric artery in intrahepatic cholangiocarcinoma: A case report.
    Myeong Hun Oh, Byeong Gwan Noh, Hyung Il Seo, Young Mok Park, Suk Kim, Nam Kyung Lee, Seung Baek Hong.
      Intrahepatic cholangiocarcinoma (IHCC) is the second most common primary liver malignancy after hepatocellular carcinoma and is associated with a poor prognosis. Although surgical resection remains the only potentially curative treatment, the 5-year survival rate is <30%. Among various prognostic factors, perineural invasion (PNI) is considered noteworthy. Multidetector computed tomography (MDCT) plays a critical role in the diagnosis and staging of IHCC and may aid in the detection of PNI. The current study presents the clinical course and radiological findings of an 82-year-old woman with IHCC who showed PNI around the superior mesenteric artery, highlighting the importance of preoperative MDCT evaluation.
    Keywords:  case reports; cholangiocarcinoma; multidetector computed tomography; perineural invasion
    DOI:  https://doi.org/10.3892/ol.2026.15658
  6. Cancer Treat Res Commun. 2026 May 27. pii: S2468-2942(26)00177-2. [Epub ahead of print]48 101266
    Patient survival outcomes in brain metastases of pancreatic ductal adenocarcinoma: A comprehensive analysis.
    Yuanchi Ma, Boyang Li, Zhenchao Gao, Zheng Wang, Liang Han, Kongyuan Wei, Hairong He.
       BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) often presents with metastases. Brain metastases are rare, necessitating a thorough analysis of patient profiles and management.
    METHODS: Patients with PDAC and brain metastases (2010-2021) were identified from the SEER database. PDAC-specific survival (PSS) was the primary outcome. Survival differences were assessed via Kaplan-Meier analysis, and prognostic factors via Cox regression.
    RESULTS: This study included 113 patients with PDAC brain metastasis, and survival analysis was conducted on 78 eligible patients. The median PSS times were 6 months for brain metastases combined with lung metastases, 5 months for brain-only metastases, 3 months for brain metastases combined with bone metastases, 2 months for brain metastases combined with multiple metastases, and 1.5 months for brain metastases combined with liver metastases. Patients who received both radiotherapy and chemotherapy had better prognoses than those who had received radiotherapy only (P < 0.001, hazard ratio (HR) = 0.110). Other risk factors were combined with liver metastases (compared with only brain metastasis: P < 0.001, HR = 4.57) and a separated, divorced, or widowed marital status (compared with a married status: P = 0.038, HR = 2.029).
    CONCLUSIONS: Patients with PDAC brain metastases combined with liver metastases showed a significantly shorter median PSS time than those with brain metastases only. Patients who had received both chemotherapy and radiotherapy had longer median PSS time than those who had received radiotherapy only. A study with a large sample size is still required.
    Keywords:  Metastatic sites; Pancreatic ductal adenocarcinoma; SEER database; Survival analysis; Treatment
    DOI:  https://doi.org/10.1016/j.ctarc.2026.101266
  7. Turk Neurosurg. 2026 ;36(3): 450-456
    Brain Metastases in Pediatric Extracranial Solid Tumors: A 20-Year Experience in Challenging a Rare Diagnosis.
    Dilek Gul, Beste M Atasoy, Burcu Tufan Tas, Adnan Dagcinar, Zerrin Ozgen.
       AIM: To investigate the clinical features, treatments, and outcomes of pediatric patients with brain metastasis from extracranial solid tumors, which has been known as a rare condition.
    MATERIAL AND METHODS: Over a 20-year period, 520 children treated for extracranial solid tumors in our radiotherapy clinic were reviewed, and 12 cases (2.2%) of brain metastases were identified. The primary tumors included neuroblastoma (n=5), osteosarcoma (n=3), Ewing sarcoma (n=2), rhabdoid tumor of the kidney (n=1), and Wilms tumor (n=1). Retrospective analysis was performed to evaluate tumor and treatment features. Overall survival was measured from the initial diagnosis. Overall survival after brain metastasis, local control, and brain metastasis progression-free survival were calculated from the time of brain metastasis diagnosis to death.
    RESULTS: Median follow-up was 31 months (range, 13-72 months). Brain metastasis developed at a median of 13 months after primary diagnosis (range, 3-69 months). Most brain metastases were supratentorial and solitary, with nine of 12 patients (75%) having solitary lesions and eight of 12 (67%) having supratentorial lesions. Surgical excision was performed in 9 patients (75%). Radiotherapy was administered locally (20-30 Gy, n=7) or to the craniospinal axis (21.6 or 23.4 Gy, n=2). Ten patients died during follow-up, 70% of whom did not experience cranial progression. Local control rate for irradiated lesions was 81.5% (median duration: 22 months). The brain metastasis-free survival was 71.4% (95% confidence interval [CI]: 2.59%-55.41%) with a median of 10 (range, 1-41) months. The 2-year survival rate was 58.3% (95% CI: 6.15%-71.84%). The 2-year overall survival rate after brain metastasis was 16.7% (95% CI: 7.13%-21.53%).
    CONCLUSION: Brain metastasis remains rare in pediatric solid tumors. Most patients died from extracranial disease progression rather than cranial relapse. Radiotherapy can effectively relieve symptoms and may delay the progression of brain metastasis. Guidelines may help optimize the treatment of patients with brain metastasis.
    DOI:  https://doi.org/10.5137/1019-5149.JTN.49617-25.5
  8. J Psychosoc Oncol. 2026 Jun 05. 1-36
    Depression as a potential early indicator of pancreatic cancer: a systematic review of prevalence, mechanisms, and temporal associations.
    Melissa Frangie Machado, Niloofar Masoumi, Leila Azari, Megan Centrella, Kami Mukenschnabl, Yu Chen Lin, Pamela Hodul, Jessica Y Islam, Kea Turner, Amir Alishahi Tabriz.
       BACKGROUND: Pancreatic cancer (PC) remains one of the most lethal malignancies, with a five-year survival rate of only 12%, largely due to late diagnosis. Depression is frequently reported in PC and may precede its onset, yet underlying mechanisms remain unclear.
    AIMS: This systematic review examined (1) the prevalence of depression in PC, (2) potential psychological, clinical, and biological mechanisms, and (3) the temporality of depressive symptoms relative to PC diagnosis.
    METHODS: Following PRISMA guidelines, EMBASE, MEDLINE, Web of Science, and Cochrane were searched through February 2025 (PROSPERO: CRD42022378830). Studies including adults with PC assessing depression or related biomarkers were analyzed.
    RESULTS: Twenty-six studies met inclusion criteria. Depression prevalence ranged 3.5-51.8%. Six studies reported depressive symptoms often preceding diagnosis by 3-6 months. Biomarker studies identified elevated IL-6, CRP, and kynurenine-tryptophan pathway alterations.
    CONCLUSIONS: Depression may represent a paraneoplastic or early manifestation of PC. Further prospective, mechanistic studies are warranted.
    Keywords:  Biomarkers; cancer; depression; early detection of cancer; gastrointestinal cancers; oncology; pancreatic cancer; paraneoplastic syndromes; quality of life; risk factors
    DOI:  https://doi.org/10.1080/07347332.2026.2679587
  9. Brain Behav Immun. 2026 Jun 01. pii: S0889-1591(26)00589-1. [Epub ahead of print] 106841
    Mammary tumors-derived exosomes induce striatal NF-κB signaling, microglial reactivity, and anxiety/depression-like behaviors.
    Yuan-Yuan Han, Ji-Chao Wu, Hong-Mei Yang, Zhi-Wei Guo, Chen-Qiong Gu, Ya-Wen Deng, Hui-Dong Li, Min-Hua Huang, Xue-Ping He, Qi-Jia Han, Heng Kong, Yan-Qi Xu, Jian Yao, Peng-Hui Shan, Hong-Yun Chen, Jia-Yue Wen, De-Xiang Liu, Ya-Mei Tang, Zhang Wang, Cheng Long.
      Emerging evidence links peripheral cancer growth with affective disturbances, yet the mechanisms bridging tumor biology and central dysfunction remain poorly defined. In a cohort of newly diagnosed breast cancer patients and healthy controls, patients exhibited elevated depressive and anxiety-related symptoms, accompanied by a focal reduction of amplitude of low-frequency fluctuations (ALFF) in the right caudate. The ALFF of right caudate is negatively correlated with individual affective scores, suggesting early striatal involvement in cancer-related affective vulnerability. Building on these observations, we used mammary tumor-bearing mouse models and found that mammary tumor-bearing mice developed pronounced anxiety/depression-like behaviors accompanied by microglial reactivity and heightened NF-κB signaling in the striatum. In vitro, exosomes isolated from mammary tumor-bearing cells activated BV-2 microglia and the NF-κB pathway, and enhanced pro-inflammatory cytokine production. Systemic administration of tumor cell-derived exosomes in naïve mice reproduced both behavioral abnormalities and striatal microglial/NF-κB activation, whereas pharmacological inhibition of exosome release in mammary tumor-bearing mice ameliorated behavioral abnormalities and reduced neuroinflammation. Together, these human and experimental data identify exosomes as a mechanistic conduit linking peripheral malignancy to central affective pathology. Exosome-driven NF-κB activation in striatal microglia emerges as a key driver of cancer-associated anxiety and depression. It represents a potential therapeutic point for mitigating neuropsychiatric comorbidity in cancer.
    Keywords:  Anxiety and depression; Exosome; Mammary tumor; Microglia; NF-κB pathway
    DOI:  https://doi.org/10.1016/j.bbi.2026.106841
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