Impact of treatment history on drug resistance of metastatic colorectal cancer organoids

作者：Maarten A. Huismans, Lidwien P. Smabers, Sascha R. Brunner, Arne van Hoeck, Demi van de Kaa, Ingrid A. Franken, G. Emerens Wensink, Jan Köster, Richard Volckmann, Onno Kranenburg, Miriam Koopman, Hugo J.G. Snippert, Jeanine M.L. Roodhart · 发表于：iScience · 年份：2025 · DOI：10.1016/j.isci.2025.113801 · 被引用次数：2 · 研究领域：Colorectal Cancer Treatments and Studies、Intraperitoneal and Appendiceal Malignancies、Cancer therapeutics and mechanisms

, and Hedgehog pathway enrichment. Acquired resistance to 5-FU and irinotecan was only partially captured, with irinotecan resistance linked to specific mutational signatures and deep deletions in common fragile sites, associated with distinct gene expression profiles. Our findings reveal that PDOs capture chemotherapy-induced genomic and phenotypic changes differently depending on the drug, suggesting varied mechanisms of acquired resistance involving both tumor cell-intrinsic properties and dynamic tumor cell states.