bims-netuvo 2026-01-25 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–01–25
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Peripheral Nerves in Cancer: Regulatory Roles and Therapeutic Strategies.
Perineural spread as the presenting symptom for cutaneous squamous cell carcinoma.
DACIT device for axon cancer cell interaction testing in 2D and 3D.
Altered spatial patterns of intrinsic brain activity and cognitive decline in colorectal cancer survivors.
Biology of Brain Metastases.
Preoperative Prediction of Perineural Invasion and Survival in Gastric Cancer Using Extracellular Volume Fraction and Dual-Energy CT Quantitative Parameters: A Dual-Center Study.
Construction and validation of a risk prediction model for perineural invasion in early gastric cancer based on multivariate analysis.
Survival of lung cancer patients with central nervous system metastases: from clinical trials to mouse models.
Individualized prediction of brain metastasis risk in patients with breast cancer.
A real-world study on clinical features and prognosis of Chinese breast cancer patients with brain metastases.
Limitations in Study Design and Stratification in Phase II Stereotactic Radiosurgery Trial for Small Cell Lung Cancer Brain Metastases.

MedComm (2020). 2026 Feb;7(2): e70594

Peripheral Nerves in Cancer: Regulatory Roles and Therapeutic Strategies.

Yan Fu, Zhi-Shan Ge, Qing-Yue Cao, Zi-Han Li, An Zhang, Hai-Dong Zhu, Gao-Jun Teng.

  Cancer neuroscience has emerged as a transformative frontier in oncology research, focusing on the interplay between cancer cells and the nervous system. Cancer cells establish tumorspecific neural networks within tumor tissues via neurotrophic hijacking. The nervous system regulates tumor initiation, progression, and metastasis either directly by regulating signal transduction in tumor cells or indirectly by modulating the tumor microenvironment (TME). The positive feedback loop between cancer cells and nerves promotes tumor progression. Deciphering the regulatory role of nerves in tumor progression may yield novel anticancer therapeutic options. In this review, the interaction between nerves and cancer cells is described, including how cancer cells hijack and remodel nervous system structure and function, and how neuron-signaling regulates cancer cell growth directly or indirectly through modulating the TME. This evidence of the critical role of nerves in the malignant phenotype of tumors indicates the potential of using neuron-signaling targeting strategies in cancer treatment. By summarizing these findings, this review aims to provide comprehensive insights into the interaction between nerves and cancer cells, paving the way for neuron-signaling-based anticancer therapies.

Keywords:  cancer; interaction; mechanism; nerve; therapeutic strategies

DOI:  https://doi.org/10.1002/mco2.70594
JAAPA. 2026 Feb 01. 39(2): 32-35

Perineural spread as the presenting symptom for cutaneous squamous cell carcinoma.

Katey Wert, Brittany Andress.

   ABSTRACT: Recurrent cutaneous squamous cell carcinoma (cSCC) may rarely present with symptoms of perineural spread (PNS) or perineural invasion (PNI), which may not be noted on initial pathology. Because PNS can mimic benign neuropathies, patients with this manifestation often experience diagnostic delays, especially when PNI is not initially detected. This case report describes a patient who experienced persistent and progressive neurologic symptoms for more than a year before imaging revealed recurrent cSCC involving the cervical nerve roots, despite initial evaluations and imaging failing to detect PNS or PNI. It highlights the need to closely follow and perform repeat evaluations for patients with persistent symptoms without a definitive diagnosis.

Keywords:  adjuvant radiation; cutaneous squamous cell carcinoma; dysesthesia; paresthesia; perineural invasion; perineural spread

DOI:  https://doi.org/10.1097/01.JAA.0000000000000292
iScience. 2026 Feb 20. 29(2): 114557

DACIT device for axon cancer cell interaction testing in 2D and 3D.

Ines Velazquez-Quesada, Vahid Alizadeh, Kara Allison, Elizaveta Belova, Svetllana Kallogjerovic, Natasha Hesketh, Xiaotian Zhang, Gareth Thomas, Erkan Tüzel, Bojana Gligorijevic.

  Peripheral innervation is increasingly recognized as a critical regulator of tumor progression, yet in vitro models that enable controlled study of axon-cancer cell interactions remain limited. Here, we present the Device for Axon-Cancer cell Interaction Testing in 2D and 3D (DACIT), a microfluidic platform that spatially separates neuronal somas from axons and cancer cells. This configuration supports experimental designs where compartments can be exposed to either identical or distinct conditions. Moreover, the channel height allows the incorporation and monitoring of tumor spheroids, enabling quantification of tumor growth and 3D invasion. We demonstrate DACIT compatibility with common cellular assays, including immunofluorescence, invadopodia assays, pharmacological perturbations, live-cell imaging, and 3D spheroid invasion. Together, these features establish DACIT as a versatile tool to interrogate how peripheral axons influence cancer cell behavior.

Keywords:  Biological sciences; Cancer; Cell biology; Neuroscience

DOI:  https://doi.org/10.1016/j.isci.2025.114557
J Cancer Surviv. 2026 Jan 21.

Altered spatial patterns of intrinsic brain activity and cognitive decline in colorectal cancer survivors.

Brian Ellis, John Quan Nguyen, Ian Ray, Tara Riddle, Ashley Hill, Robert Yu, Kendrith Rowland, Zhaoyue Shi.

   PURPOSE: Cancer-related cognitive impairment (CRCI) is a common and debilitating complication among colorectal cancer survivors, even in those without chemotherapy exposure. To identify cancer-related neural changes, we investigated spontaneous brain activity and cognition in colorectal cancer survivors using cognitive assessments and resting-state functional magnetic resonance imaging (rsfMRI).
METHODS: Nineteen survivors (stages I-II, cancer diagnosis < 12 months, chemotherapy-naïve) and 18 healthy controls underwent a battery of objective/subjective cognitive tests and MRI. RsfMRI data was analyzed with fractional amplitude of low-frequency fluctuations (fALFF) and functional connectivity (FC). Statistical analysis was controlled for age, sex, education, depression, and anxiety, with multiple comparison correction.
RESULTS: Compared to controls, survivors performed significantly worse on the Hopkins Verbal Learning Test (HVLT-R) Recognition Discrimination Index (RDI) (p = 0.03) and showed slower psychomotor speed on the Trail Making Test (TMT-A) (p = 0.02). RsfMRI analysis revealed increased fALFF in the right hippocampus and bilateral inferior/middle temporal, parahippocampal, and fusiform gyri, with decreased fALFF in the bilateral superior/middle frontal gyri and left inferior frontal gyrus. RDI was negatively correlated with fALFF in right temporal regions. Survivors also exhibited reduced FC within the default mode network (DMN) (p < 0.05).
CONCLUSIONS: This cross-sectional study shows that colorectal cancer survivors display hyperactivity in the temporal regions and disrupted DMN connectivity associated with cognitive decline, suggesting a maladaptive neural response.
IMPLICATIONS FOR CANCER SURVIVORS: Our study identified the functionally altered brain regions and networks associated with colorectal CRCI using MRI. This would provide potential biological targets for developing interventions such as neuromodulation for mitigating the adverse effects of colorectal CRCI.

Keywords:  Cancer-related cognitive impairment (CRCI); Colorectal cancer; Fractional amplitude of low-frequency fluctuation (fALFF); Functional connectivity; Magnetic resonance imaging (MRI)

DOI:  https://doi.org/10.1007/s11764-025-01963-6
Cancer J. 2026 Jan-Feb 01;32(1):pii: e0802. [Epub ahead of print]32(1):

Biology of Brain Metastases.

Ozum Atasoy, Eyub Y Akdemir, Rupesh Kotecha.

  Brain metastases affect up to 40% of patients with cancer and represent a major clinical challenge. Despite advances in surgery, radiotherapy, and systemic therapies, outcomes remain modest, partly due to the blood-brain barrier and the limited penetration of systemic therapies. Brain metastasis formation involves a complex sequence of events, including hematogenous spread, blood-brain barrier transmigration, and adaptation to neural niches. Recent multi-omics studies have revealed that brain metastases undergo substantial genomic, epigenetic, and transcriptomic divergence from primary and extracranial tumors. These changes promote immune evasion, metabolic reprogramming, and resistance to therapy. Tumor-glia interactions and vascular co-option further sustain metastatic progression. As conventional molecular profiling often fails to capture central nervous system-specific alterations, site-specific biopsies and liquid biopsies are gaining importance. This review provides a comprehensive overview of the molecular and cellular mechanisms underlying brain metastases and outlines emerging avenues for targeted interventions.

Keywords:  biology; brain metastases; metastasis mechanisms; metastatic cascade; perivascular niche; tumor microenvironment

DOI:  https://doi.org/10.1097/PPO.0000000000000802
Acad Radiol. 2026 Jan 20. pii: S1076-6332(26)00004-8. [Epub ahead of print]

Preoperative Prediction of Perineural Invasion and Survival in Gastric Cancer Using Extracellular Volume Fraction and Dual-Energy CT Quantitative Parameters: A Dual-Center Study.

Mengyue Zhang, Mimi Mao, Haipeng Gong, Dandan Ji, Xian Fan, Tianle Wang, Zhengqi Zhu.

   RATIONALE AND OBJECTIVES: This study aimed to develop a nomogram integrating extracellular volume fraction (ECV), dual-energy CT (DECT) quantitative parameters, and morphological features to predict perineural invasion (PNI) and recurrence-free survival (RFS) in gastric cancer (GC).
MATERIALS AND METHODS: We retrospectively collected GC patients' data from two centers. Two radiologists independently assessed ECV, DECT quantitative parameters, and morphological features. Multivariate logistic regression analyses were performed to identify independent risk factors for PNI and construct a predictive nomogram. The nomogram's predictive performance was evaluated using calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Multivariate Cox regression analyses were conducted to determine independent prognostic factors for RFS. Kaplan-Meier survival curves were generated to compare RFS between nomogram predicted PNI-positive and PNI-negative groups.
RESULTS: A total of 268 patients were included in the analysis, with 166 in the training cohort and 102 in the validation cohort. ECV, NICdelay, and ctEMVI were identified as independent risk factors for PNI. The nomogram demonstrated good predictive performance for PNI, with area under the ROC curve (AUC) of 0.822 and 0.810 in the training and validation cohorts. Calibration curves indicated good agreement between predicted and observed PNI, and DCA demonstrated clinical utility. Nomogram-predicted PNI was an independent prognostic factor for RFS, with the predicted PNI-positive group exhibiting significantly lower RFS rate than the predicted PNI-negative group.
CONCLUSION: A nomogram integrating ECV, DECT quantitative parameters, and morphological features could effectively predict PNI in GC and provide significant prognostic value for postoperative RFS.
KEY POINTS:

Keywords:  Dual-energy CT (DECT); Extracellular volume fraction (ECV); Gastric cancer; Perineural invasion (PNI); Prediction

DOI:  https://doi.org/10.1016/j.acra.2026.01.006
BMC Cancer. 2026 Jan 19.

Construction and validation of a risk prediction model for perineural invasion in early gastric cancer based on multivariate analysis.

Guangxu Zhu, Shengjie Zhou, Jianjun Qu, Xuguang Jiao, Yanpeng Gao, Xiaomeng Wang.

   OBJECTIVE: We aimed to identify independent risk factors for perineural invasion (PNI) in early gastric cancer (EGC) and to construct the first individualized nomogram for predicting PNI risk.
METHODS: We retrospectively analyzed clinicopathological data from 416 EGC patients who underwent radical gastrectomy between December 2019 and August 2025. The optimal set of risk predictors for PNI was selected using the LASSO regression model with ten-fold cross-validation. Independent risk factors were subsequently identified via multivariable logistic regression analysis. For internal validation, we randomly selected 30% of the sample as a validation set using R software (version 4.4.2). The model's performance was comprehensively evaluated by assessing its discrimination (area under the receiver operating characteristic curve, AUC), calibration (Hosmer-Lemeshow test and calibration curve), and clinical utility (decision curve analysis, DCA).
RESULTS: A total of 416 patients were included in the final analysis, among whom 30 (7.21%) had PNI. LASSO regression analysis identified eight predictors for PNI: age, CEA level (ng/mL), tumor location, maximum tumor thickness, tumor differentiation, lymphovascular invasion, Lauren classification, and pT stage. These variables were subsequently incorporated into a multivariable logistic regression model. The analysis revealed that age (OR = 1.105, 95% CI: 1.029-1.187, P = 0.006), CEA level (OR = 59.489, 95% CI: 3.456-1023.871, P = 0.005), maximum tumor thickness (OR = 38.807, 95% CI: 3.408-441.872, P = 0.003), and lymphovascular invasion (OR = 4.131, 95% CI: 1.337-12.768, P = 0.014) were independent risk factors for PNI in EGC (all P < 0.05). The nomogram demonstrated strong discriminative ability, with AUC values of 0.895 (95% CI: 0.839-0.950) in the training cohort and 0.783 (95% CI: 0.625-0.940) in the validation cohort. The Hosmer-Lemeshow test indicated good model calibration in both the training (χ² = 11.994, P = 0.152) and validation cohorts (χ² = 3.833, P = 0.872). DCA showed substantial clinical net benefits across a wide range of threshold probabilities.
CONCLUSION: In conclusion, this study identified age, CEA level, maximum tumor thickness, and lymphovascular invasion as independent predictors of PNI in EGC. We developed the first nomogram for individualized PNI risk assessment, which demonstrated strong predictive performance, good calibration, and clinical usefulness. Although this tool offers a reliable approach for personalized risk evaluation, further multicenter validation is necessary to enhance its clinical applicability.

Keywords:  EGC; Multivariate analysis; Perineural invasion; Risk prediction model

DOI:  https://doi.org/10.1186/s12885-026-15583-5
Clin Transl Oncol. 2026 Jan 23.

Survival of lung cancer patients with central nervous system metastases: from clinical trials to mouse models.

Hainan Yang, Chengji Wang, Hui Ye, Tao Lin, Weifang Yuan, Changguo Shan, Qingjun Hu, Xin Jin, Da Liu, Lei Wen, Ming Lei.

   BACKGROUND: Central nervous system (CNS) metastasis is common in patients with non-small cell lung cancer (NSCLC) and is associated with poor prognosis. Evidence guiding optimal clinical management remains limited, and comprehensive studies on animal models that recapitulate different CNS metastatic patterns are lacking.
METHODS: A total of 316 NSCLC patients with CNS metastases were retrospectively enrolled between May 2019 and February 2024. Patients were categorized into four groups: brain metastases only (BM, n = 145), leptomeningeal metastases only (LM, n = 43), concurrent brain and leptomeningeal metastases (BM+LM, n = 62), and brain metastases preceding leptomeningeal metastases (BM-LM, n = 66). Overall survival was analyzed using survival curves. To explore the distinct biological processes underlying BM and LM, mouse models of brain metastasis were established using tail vein, internal carotid artery, and left ventricular injection methods.
RESULTS: Survival analysis demonstrated that patients with LM had significantly shorter overall survival compared with those with BM alone (P < 0.05). Patients with concurrent BM and LM also exhibited poorer overall survival than those in whom BM preceded LM (P < 0.01). In animal experiments, brain metastasis developed in one of five mice following tail vein injection, one of five following internal carotid artery injection, and two of five following left ventricular injection, indicating the highest success rate with the latter approach. None of the animal models successfully reproduced the sequential progression from brain metastasis to leptomeningeal metastasis.
CONCLUSION: Leptomeningeal involvement in NSCLC is associated with significantly worse survival outcomes compared with brain metastasis alone. Although several injection strategies can generate brain metastasis in mice, current models fail to simulate the transition from brain metastasis to leptomeningeal metastasis, highlighting the need for improved and more representative animal models.

Keywords:  Animal models; Brain metastasis; Leptomeningeal metastases

DOI:  https://doi.org/10.1007/s12094-025-04125-3
J Neurooncol. 2026 Jan 22. 176(3): 179

Individualized prediction of brain metastasis risk in patients with breast cancer.

Gino Cioffi, Kristin Waite, Ancha Baranova, Jill S Barnholtz-Sloan.



Keywords:  Brain metastases; Breast cancer; Cumulative incidence; Genomic; Nomogram; Risk

DOI:  https://doi.org/10.1007/s11060-026-05433-6
Front Oncol. 2025 ;15 1497269

A real-world study on clinical features and prognosis of Chinese breast cancer patients with brain metastases.

Hong-Dan Chen, Xiao-Wen Liao, Xiao-Geng Chen, Yu-Nan Su, Ding-Long Pan, Guo-Zhong Chen, Min Wu, Shuang-Long Cai.

   Background: This study aimed to analyze the clinical characteristics and prognosis of breast cancer (BC) patients with brain metastases (BM).
Methods: We performed a retrospective analysis of breast cancer patients with brain metastases (BCBM) in a real-world setting.
Results: In a cohort of 249 breast cancer brain metastasis (BCBM) patients (all female; median age 46 years), molecular subtypes were distributed as follows: luminal (38.95%), HER2-positive (32.93%), and triple-negative (28.11%). Distinct metastatic patterns were observed: luminal subtype correlated with bone metastases (55.73%, p<0.001), HER2-positive with liver metastases (46.34%, p<0.001), and luminal with leptomeningeal metastases (19.59%, p=0.002). For CNS-directed treatment, 70.28% received radiotherapy (69.71% whole-brain radiotherapy, 30.28% stereotactic radiosurgery), while 23.69% received no local treatment. After median follow-up of 63.1 months, 81.52% had died. Multivariable analysis identified HER2-positive subtype and brain metastasis as first metastatic site as protective for overall survival after brain metastasis (OS-BM), while leptomeningeal metastasis were independent risk factors.
Conclusion: This study reveals distinct patterns of metastatic spread across breast cancer molecular subtypes and identifies key prognostic factors for survival after brain metastasis. The findings underscore the critical influence of tumor biology on disease progression and outcomes, highlighting the need for subtype-specific management strategies in BCBM patients.

Keywords:  brain metastases; breast cancer; clinical features; prognosis; real-world study

DOI:  https://doi.org/10.3389/fonc.2025.1497269
J Clin Oncol. 2026 Jan 20. JCO2501729

Limitations in Study Design and Stratification in Phase II Stereotactic Radiosurgery Trial for Small Cell Lung Cancer Brain Metastases.

Orhun Akdogan, Kubra Canaslan, Buket Hamitoglu, Ozan Yazici, Osman Sutcuoglu.

DOI: https://doi.org/10.1200/JCO-25-01729