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Challenges and Limitations of Generative AI in Synthesizing Wearable Sensor Data
Harnessing cuproptosis for pancreatic cancer therapy: From molecular insights to clinical prospects
Biomed Pharmacother. 2025 Dec 2;193:118852. doi: 10.1016/j.biopha.2025.118852. Online ahead of print.
ABSTRACT
Pancreatic cancer (PC) remains a high-fatality malignancy with limited clinical progress, characterized by aggressive biology, marked resistance to standard therapies, and dismal outcomes. Even with state-of-the-art resection, radiotherapy, and multidrug chemotherapy, median survival benefits are modest, highlighting an urgent need for mechanism-based interventions. Cuproptosis, a newly delineated modality of regulated cell death initiated by intracellular copper accumulation and mitochondrial stress, presents a biologically coherent therapeutic avenue. Distinct from apoptosis, necroptosis, and ferroptosis, cuproptosis is driven by the direct binding of copper to lipoylated enzymes of the tricarboxylic acid (TCA) cycle, resulting in bioenergetic failure, misfolded protein aggregation, and collapse of cytotoxic proteostasis. Converging studies suggest that copper disequilibrium and metabolic reprogramming are recurrent features of PC, potentially contributing to malignant progression, immune evasion, and chemoresistance. These insights motivate two complementary strategies: first, therapeutic manipulation of copper flux, via chelators, ionophores, or transport modulators, to selectively trigger cuproptosis in tumor cells; and second, sensitization of mitochondrial metabolism, through targeting lipoic-acid pathway components, pyruvate utilization, or TCA load, to lower the threshold for cuproptotic killing. In parallel, multi-omic interrogation of cuproptosis-associated genes, proteins, and metabolites may yield prognostic and predictive biomarkers, enabling risk-adapted treatment selection and rational combinations with cytotoxic, targeted, or immunotherapeutic modalities. This review synthesizes recent advances on cuproptosis in PC and outlines its translational potential as both a therapeutic target and a biomarker framework.
PMID:41337879 | DOI:10.1016/j.biopha.2025.118852
A Framework for Causal Concept-based Model Explanations
Digital Biometrics in Predicting Risk for Obstructive Sleep Apnea and Hypertension: Decentralized, Prospective Cohort Study
Multi-omic profiling provides insights into the heterogeneity, microenvironmental features, and biomarker landscape of small-cell lung cancer
Mol Cancer. 2025 Dec 2. doi: 10.1186/s12943-025-02514-4. Online ahead of print.
ABSTRACT
BACKGROUND: Greater understanding of differential therapeutic sensitivity, specifically to immunotherapy, in small-cell lung cancer (SCLC) is required.
METHODS: We explored SCLC heterogeneity through integrated molecular characterization of tumor tissue samples from 159 treatment-naive patients, utilizing genetic, epigenetic, transcriptional, and proteomic profiling, immunohistochemistry staining for multiple biologically relevant markers including transcriptional subtype-defining proteins, and spatial immune profiling using multiplex immunofluorescence.
RESULTS: Multi-omics analysis confirmed high heterogeneity across/within neuroendocrine and non-neuroendocrine subtypes. Methylomics analysis identified four methylome clusters that may enhance subtype prediction, prognosis, and longitudinal monitoring of subtype evolution. Immunohistochemistry analysis showed high MHC-I expression in non-neuroendocrine subtypes, which have greatest potential benefit from adding immunotherapy to chemotherapy; high DLL3 expression associated with neuroendocrine subtypes and an immune-cold tumor microenvironment. Multiplex immunofluorescence demonstrated associations of MHC-I with spatial arrangement and phenotypic features of immune cells in the tumor microenvironment of high-MHC-I-expressing SCLC, providing mechanistic rationale for MHC-I as a potential biomarker of immunotherapy response.
CONCLUSIONS: This multimodal profiling analysis provides further insights into the biologic complexity of SCLC and highlights potential therapeutic vulnerabilities of distinct disease subtypes.
PMID:41331472 | DOI:10.1186/s12943-025-02514-4
Whole-genome landscapes of 1,364 breast cancers
Nature, Published online: 03 December 2025; doi:10.1038/s41586-025-09812-3
Whole-genome and transcriptome analysis of 1,364 cases of breast cancer from South Korea broadens our understanding of breast cancer biology and reveals genomic features that connect tumour biology with treatment responses and clinical outcomes.