bims-netuvo 2025-12-07 papers

Trends Cancer. 2025 Nov 28. pii: S2405-8033(25)00280-8. [Epub ahead of print]

Neural hijacking in cancer metabolism: from nutrients to organelles.

Songhui Shin, Su Yeon Myoung, Hye Jin Cho, Seongjun Kim, Namgyu Lee, Sung Jin Park.

Tumors dynamically interact with the central and peripheral nervous systems, hijacking neural plasticity and reprogramming metabolism in a bidirectional manner to drive cancer progression. Neural inputs reshape the metabolism of cancer cells and their microenvironment - glycolysis, oxidative phosphorylation, and lipid metabolism - while tumors exploit neuronal nutrients and mitochondria to thrive under metabolic stress. This review explores neurocancer metabolic crosstalk through multiple mechanisms by three principal modes of interaction, highlighting how targeting these metabolic interdependencies could disrupt tumor progression. By integrating cancer metabolism and neuroscience, it offers a conceptual framework for understanding neural-tumor metabolic circuits in malignancy and identifies potential therapeutic vulnerabilities.

Keywords: cancer; crosstalk; metabolism; neuron; therapy

DOI: https://doi.org/10.1016/j.trecan.2025.11.006

Trends Cancer. 2025 Dec 02. pii: S2405-8033(25)00281-X. [Epub ahead of print]

The evolving landscape of brain metastasis: volume II.

Manuel Valiente, Carey Anders, Adrienne Boire, Benjamin Izar, Nuria Kotecki, Srinivas Malladi, Joan Massagué, Nelson S Moss, Josh Neman, Matthias Preusser, Sanne Schagen, Peter M Siegel, Hussein Tawbi, Varun Venkataramani, Frank Winkler, Gelareh Zadeh, Johanna A Joyce.

Brain metastasis (BrM) represents the most common intracranial malignancy, arising in up to 30% of all adult cancer patients and contributing significantly to cancer-related morbidity and mortality. BrM is now recognized as a biologically distinct condition with unique mechanisms of organotropism, colonization, and therapeutic vulnerability. We highlight recent progress in omic and spatial profiling, which has revealed key drivers of brain tropism. These findings have reshaped therapeutic strategies, leading to clinical trials that specifically address central nervous system (CNS) involvement. Emerging approaches now include efforts to prevent brain relapse. Preclinical models increasingly provide sophisticated platforms to evaluate next-generation therapies. Collectively, these advances are transforming the clinical landscape, offering new hope for the prevention and management of BrM through precision medicine and integrated therapeutic strategies.

Keywords: brain metastasis; cancer neuroscience; neuroimmunology; precision oncology; prevention; tumor microenvironment

DOI: https://doi.org/10.1016/j.trecan.2025.11.007

Cancer Res Commun. 2025 Dec 01. 5(12): 2102-2111

Association of Neuronal Autoantibodies with Overall Survival in Patients with Gastric Cancer.

Guanghui Liu, Xin Tan, Kaibiao Xu, Jingsi Liu, Qianhui Zheng, Xiaoyun Huang, Suyue Pan, Guoxin Li, Yafang Hu, Hao Liu.

Neuronal autoantibodies have been identified in immune-mediated encephalitis, most of which are related to paraneoplastic neurologic syndromes (PNS). We detected neuronal autoantibodies in patients with gastric cancer without PNS and illustrated their correlation with clinical prognosis. All serum samples were tested by the mouse brain tissue-based assay (TBA) using immunofluorescence for screening neuronal autoantibodies. Known PNS-related neuronal autoantibodies were detected by cell-based assay. A single-center cohort has been started in Nanfang Hospital. The T-cell status of the tumor microenvironment was assessed. Single-cell sequencing was performed with limited tumor samples. Patients were grouped into TBA-positive (n = 144) and TBA-negative (n = 179) groups by the TBA status. Further screening of TBA+ specimens using the cell-based assay method revealed known PNS-related autoantibodies in 13.2% (19/144) of cases. Additionally, TBA-positive patients with gastric cancer exhibited lower CD8+ T-cell infiltration in the tumor tissue. The survival analysis show that neuronal autoantibodies in patients (TBA-positive) were associated with shorter overall survival (OS; P = 0.014). In the multivariate survival analysis, TBA positivity was still associated with shortened OS after adjusting the major covariates (HR = 2.28; 95% confidence interval, 1.31-3.97; P = 0.004). Meanwhile, single-cell sequencing indicates that cell junction assembly and synapse organization may play important roles in biological process. In this cohort study, neuronal autoantibodies were highly prevalent among patients with gastric cancer and were associated with shortened OS and features of immunosuppression within the tumor microenvironment, suggesting a candidate for exploring therapeutic relevance, with further mechanistic studies needed for validation.
SIGNIFICANCE: Neuronal autoantibodies are prevalent in patients with gastric cancer, and patients without neurologic symptoms are linked to shorter survival and immunosuppression. These results provide a new direction for prognostic biomarkers and targeted therapy exploration.

DOI: https://doi.org/10.1158/2767-9764.CRC-25-0495

BMC Cancer. 2025 Dec 05.

LYN mutations in breast cancer: hypothesis-generating evidence for an association with central nervous system metastasis and domain-level insights.

Elif Kardelen Çağdaş, Berkay Çağdaş.

OBJECTIVES: Central nervous system (CNS) metastasis is a major driver of morbidity in metastatic breast cancer, yet the molecular determinants of CNS tropism remain incompletely defined. LYN, a Src-family kinase integrating receptor tyrosine kinase and integrin signaling, is a biologically plausible mediator of metastatic traits.
DESIGN: We performed a retrospective, multi-study analysis of publicly available breast cancer cohorts aggregated in cBioPortal. After harmonization and de-duplication, LYN status was determinable in 5,947 invasive carcinoma of no special type (NST) tumors across 29 studies. The primary endpoint was CNS metastasis at any time (Yes/No), harmonized via a prespecified controlled vocabulary (case-insensitive substring mapping). Somatic LYN variants (coding SNVs/indels) were collapsed to patient-level classes (missense-only; truncating if any nonsense/frameshift/splice). Variants with resolvable positions were mapped to Src-family modules (SH4/Unique, SH3, SH2, SH2-kinase linker, kinase). Two-group comparisons used two-sided Fisher's exact tests with exact 95% CIs; domain screens used omnibus χ² and Benjamini-Hochberg FDR control. A prespecified Firth logistic model evaluated truncating vs. missense within LYN-mutant tumors. SETTING: Public cancer genomics repositories (cBioPortal); multi-institutional cohorts.
PARTICIPANTS: 5,947 tumors across multi-study cohorts with LYN status available.
INTERVENTIONS: None.
MAIN OUTCOME MEASURES: Primary: ever-CNS metastasis (yes/no). Secondary: distribution of LYN variant classes and domains (SH4/Unique, SH3, SH2, linker, kinase). RESULTS: CNS metastasis occurred in 5/46 (10.9%) LYN-mutated tumors vs. 110/5,901 (1.9%) LYN wild-type tumors (odds ratio (OR) = 6.42; 95% confidence interval (CI), 2.49-16.56; p = 0.0018). The endpoint was captured as ever vs. never CNS involvement (event dates unavailable), precluding time-to-event inference. Within LYN-mutant cases, an exploratory domain analysis indicated that distributions differed by CNS status (omnibus χ² p ≈ 0.014); a one-versus-rest signal at the SH4/Unique N-terminus was nominally significant and borderline after false discovery rate (FDR) (unadjusted p ≈ 0.010; q ≈ 0.052; small in-domain n = 3). By mutation class, truncating vs. missense showed a higher CNS-positive proportion (28.6% vs. 7.9%) but did not reach significance (Fisher p = 0.166; alternatively framed OR = 4.22; exact 95% CI, 0.58-30.75; p = 0.182). Firth estimates were directionally consistent with wide profile CIs under sparse counts.
CONCLUSIONS: Across pooled cohorts, LYN mutation is associated with increased odds of CNS metastasis, and domain context appears informative, with a small-sample, FDR-borderline enrichment at the SH4/Unique N-terminus. The truncating-class signal is exploratory given limited power. Signals by domain (notably SH4/Unique) are exploratory and require independent validation in larger, uniformly annotated datasets. Given small mutant denominators and ever-CNS endpoint capture, findings are hypothesis-generating and not actionable for risk stratification or treatment selection. Results motivate domain-aware annotation in future validation studies and mechanistic work.

Keywords: Breast cancer; CBioPortal; CNS metastasis; Domain mapping; Firth logistic; Fisher’s exact; LYN; SH4/Unique; Src-family kinase

DOI: https://doi.org/10.1186/s12885-025-15398-w

Health Psychol Rev. 2025 Dec 03. 1-27

The relationship between psychological stress and cancer incidence: a systematic review and meta-analysis.

Sergio Iván Galicia Pacheco, Dafina Petrova, Dunia Garrido, Andrés Catena, Blanca Madrid Pérez-Esparza, Carla Torralba, Julia Ruiz-Vozmediano, Javier García-Pérez, María José Sánchez, Rocio Garcia-Retamero.

This systematic review of prospective studies examined whether psychological stress-conceptualised as cumulative stressful life events or perceived stress-is associated with cancer incidence. It was pre-registered in PROSPERO (IDCRD42020175681) and conducted following PRISMA guidelines. Methodological quality was assessed using the NIH Tool for Observational Studies, and the certainty of evidence was assessed using the GRADE tool. Hazard ratios were synthesised using random-effects meta-analyses. Nineteen studies were included, evaluating the effect of stressful life events (k=6) and/or perceived stress (k=15) on overall (k=3), breast (k=10), prostate (k=3), colorectal (k=2) and endometrial (k=1) cancer. Neither stressful life events nor perceived stress was consistently associated with cancer risk. Conflicting results emerged for perceived stress, including both protective and detrimental effects, particularly for breast and colorectal cancer. Most studies employed non-validated stress measures (k=12), assessed stress only once (k=17), and did not examine its impact comprehensively (k=11). The certainty of evidence was graded as very low. This review found no consistent evidence linking psychological stress to cancer risk. More high-quality prospective studies using comprehensive and validated measures of psychological stress and exploring potential moderators can help advance knowledge on the role of psychological stress in cancer incidence.

Keywords: Cancer; life change events; perceived stress; psychological stress; stressful life events

DOI: https://doi.org/10.1080/17437199.2025.2590491

Brain Res Bull. 2025 Dec 02. pii: S0361-9230(25)00482-4. [Epub ahead of print]234 111670

Alterations in dynamic regional homogeneity and functional connectivity in lung cancer patients with bone metastasis pain.

Yu Tang, Tan Cheng, Lin Tang, Xiaoyu Zhou, Jing Zhang, Yong Tan, Hong Yu, Jing Yang, Daihong Liu, Jiuquan Zhang.

BACKGROUND: Although previous neuroimaging studies have characterized static brain activity in bone metastasis pain (BMP), its dynamic functional properties remain largely unexplored. This study aimed to investigate the dynamic brain activity in BMP patients.
METHODS: We analyzed dynamic regional homogeneity (dReHo) and dynamic functional connectivity (dFC) in 50 right-handed lung cancer patients with BMP(+), 36 without BMP(-), and 32 healthy controls (HCs). Spearman's correlation was used to evaluate associations with clinical variables.
RESULTS: Compared to BMP(-) patients, BMP(+) patients exhibited increased dReHo variability in the right putamen, fusiform gyrus, left middle occipital gyrus (MOG), and left cerebellar lobule VIII (cerebellum_8_L). Relative to HCs, BMP(+) patients showed increased dReHo in the cerebellum_8_L and decreased dReHo in the left anterior cingulate cortex, right inferior temporal gyrus, and frontal lobe. BMP(-) patients displayed decreased dReHo in the right rolandic operculum and putamen compared to HCs. In BMP(+) patients, dReHo variability in the left MOG was positively correlated with pain intensity, while dReHo variability in the right fusiform gyrus was negatively associated with anxiety. Enhanced dFC was observed between the right fusiform/left MOG and cerebellar subregions in BMP(+) compared to BMP(-) patients.
CONCLUSIONS: This study demonstrates abnormal dynamic brain activity within visual, affective, and sensorimotor networks in patients with BMP. These findings suggest that dReHo/dFC variability may serve as a neuroimaging biomarker for BMP diagnosis and disease monitoring. Furthermore, they provide new insights into the neurophysiological mechanisms of BMP and identify promising targets for neuromodulation-based therapeutic interventions.

Keywords: Bone metastasis pain; Dynamic functional connectivity; Dynamic regional homogeneity; Variability

DOI: https://doi.org/10.1016/j.brainresbull.2025.111670