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Context matching is not reasoning when performing generalized clinical evaluation of generative language models
npj Digital Medicine, Published online: 27 December 2025; doi:10.1038/s41746-025-02253-2
Context matching is not reasoning when performing generalized clinical evaluation of generative language modelsCancer in a drop: Liquid biopsy highlights from the World Conference on Lung Cancer (WCLC) 2025
J Liq Biopsy. 2025 Nov 29;10:100449. doi: 10.1016/j.jlb.2025.100449. eCollection 2025 Dec.
ABSTRACT
The role of liquid biopsy in oncological care continues to expand, with multiple studies presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC 2025). This review summarizes recent advances in liquid biopsy for thoracic oncology, encompassing both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). In early detection and screening, proteomic profiling has identified potential biomarkers predictive of future lung cancer risk. The integration of proteomics with clinical and imaging data can improve pulmonary nodule malignancy prediction. In resectable NSCLC, tumour-informed whole-genome sequencing (WGS) assay demonstrated high sensitivity for minimal residual disease (MRD) detection, with MRD clearance following neoadjuvant osimertinib or chemo-immunotherapy associated with favorable outcomes. In advanced NSCLC, longitudinal liquid biopsy analyses reveal dynamic subclonal evolution driving early treatment resistance. Circulating tumor DNA (ctDNA) clearance following targeted therapy in MET exon 14 skipping and BRAF-mutated tumors was associated with improved clinical outcomes. Emerging biomarkers such as ctDNA tumour fraction and circulating microRNA signatures are promising for radiotherapy stratification and prediction of immunotherapy-related toxicities. In SCLC, MRD monitoring enables earlier detection of disease progression and supports ctDNA-guided selection of patients for consolidation immunotherapy following chemotherapy. Overall, these advances demonstrate the expanding role of liquid biopsy in improving early detection, guiding treatment, and improving disease monitoring in lung cancer.
PMID:41438843 | PMC:PMC12720026 | DOI:10.1016/j.jlb.2025.100449
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Single-cell and spatial transcriptomic characterization of pulmonary pleomorphic carcinoma
Commun Biol. 2025 Dec 16;8(1):1773. doi: 10.1038/s42003-025-09162-w.
ABSTRACT
Pulmonary pleomorphic carcinoma (PPC) is a rare subtype of lung cancer that comprises both epithelial and sarcomatoid components. The molecular basis of PPC, including the cellular dynamics of its components, remains largely unknown. To elucidate potential therapeutic targets for PPC, we perform a multi-omics analysis incorporating digital spatial profiling and single-cell RNA sequencing (scRNA-seq). PPC exhibits diverse driver gene alterations, including MET exon 14 skipping mutation (METex14) and ALK fusion. In spatial transcriptomics, MET gene and protein are overexpressed exclusively within the epithelial component and not in the sarcomatoid component, even in patients harboring METex14. Epithelial-mesenchymal transition (EMT)-related transcriptional changes, along with extracellular matrix (ECM) remodeling between the epithelial and sarcomatoid components, are observed. scRNA-seq identifies cell populations within the epithelial component that contribute to the malignant transformation and differentiation of the sarcomatoid component. They are characterized by an intermediate EMT state with ECM remodeling signature, suggesting their potential as novel therapeutic targets for PPC.
PMID:41402584 | PMC:PMC12708732 | DOI:10.1038/s42003-025-09162-w