Future Oncol. 2026 Feb 20:1-14. doi: 10.1080/14796694.2026.2631302. Online ahead of print.

ABSTRACT

Gastric cancer (GC) is an epithelial malignant tumor with high morbidity and mortality. In recent years, more and more studies have strengthened our understanding of how GC develops, including the origin of GC cells, precancerous lesions, gene mutations, transcriptional changes, protein translation and the tumor microenvironment. With the concept of accurate tumor therapy gradually applied to clinical practice, these data provide more reference and basis for early prevention, early screening, early detection and accurate treatment of GC.

PMID:41717787 | DOI:10.1080/14796694.2026.2631302

Cancer Res. 2026 Feb 9. doi: 10.1158/0008-5472.CAN-25-2854. Online ahead of print.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) patients with diabetes mellitus (DM) exhibit poor clinical outcomes. Metabolic reprogramming of both cancer cells and immune compartments plays a crucial role in shaping the anti-tumor immune response in PDAC. DM-induced metabolic alteration may disrupt the intricate crosstalk between immune cells and tumor-associated immune factors, profoundly influencing PDAC progression. Here, we performed an integrated, spatially resolved multi-omics study to investigate DM-associated, cell-specific metabolic remodeling within the PDAC tumor microenvironment. DM influenced interactions between tumor cells and immune cells, which accelerated PDAC growth in both humans and mice. PDAC patients with DM exhibited higher tumor-stage, poorer differentiation, and worse outcomes. Spatial metabolic and transcriptional profiling revealed that SREBP2-dependent cholesterol biosynthesis exacerbated PDAC progression. Increased cholesterol biosynthesis promoted neutrophil recruitment and accelerated formation of neutrophil extracellular traps (NETs) by stimulating the CXCL1-CXCR1/CXCR2 signaling axis, ultimately promoting PDAC growth. Inhibition of SREBP2, pharmacological blockade of CXCL1, or perturbation of NETs markedly reduced PDAC growth in diabetic mouse models. Together, these multi-omics analyses and follow-up mechanistic studies constitute an integrated approach that elucidates a metabolic mechanism by which diabetes promotes PDAC development by remodeling the tumor immune microenvironment and highlights a potential therapeutic strategy for PDAC with DM.

PMID:41661642 | DOI:10.1158/0008-5472.CAN-25-2854

Nat Commun. 2025 Sep 25;16(1):8388. doi: 10.1038/s41467-025-63050-9.

ABSTRACT

Spatial technologies examining the cell and tissue microenvironment at near single-cell resolution are revealing important molecular insights. However, few tools enable integrated, interactive analysis of spatial-omics with tissue morphology in the same functional tissue unit. Here, we present FUSION (Functional Unit State Identification in Whole Slide Images), a web-based platform for visualizing and analyzing spatial-omics data with high-resolution histology. FUSION provides workflows for assessing cell compositions, quantitative morphometrics, and comparative tissue analyses. We demonstrate applicability across spatial assays, including 10x Visium, Visium HD, 10x Xenium, Cell DIVE, and PhenoCycler, applied to healthy and diseased tissues from kidney, small intestine, lung, and skin in the Human BioMolecular Atlas Program. FUSION is cloud-based, open-source, and accessible at https://fusion.hubmapconsortium.org/ , hosting over 50 paired datasets and tutorials. In a series of use cases, we show its capacity to distinguish renal glomeruli injury states, quantify morphometric changes, and characterize fibrosis with immune infiltration.

PMID:40998789 | PMC:PMC12462499 | DOI:10.1038/s41467-025-63050-9