Patient-Derived Organoids Predict Treatment Response in Metastatic Colorectal Cancer

作者：Lidwien P. Smabers, G. Emerens Wensink, Carla S. Verissimo, Mayke Doorn, Tao Yang, Timo Voskuilen, Maarten A. Huismans, Liselot Valkenburg‐van Iersel, Geert A. Cirkel, Elske C. Gootjes, Henk M.W. Verheul, Frank J. Jeurissen, Guus M. Bol, Hilde H. Nienhuis, Manon N.G.J.A. Braat, Edwin Cuppen, Robert G.J. Vries, Frederieke H. van der Baan, Sjoerd G. Elias, Onno Kranenburg, Miriam Koopman, Sylvia F. Boj, Jeanine M.L. Roodhart · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-1564 · 被引用次数：15 · 研究领域：Cancer Cells and Metastasis、Colorectal Cancer Treatments and Studies、Cancer Research and Treatments

PURPOSE: Accurately predicting treatment response in metastatic colorectal cancer (mCRC) is critical to avoid unnecessary toxicity and improve patient outcomes. Patient-derived organoids (PDO) are promising models, but larger prospective studies are needed to confirm their predictive value. EXPERIMENTAL DESIGN: Patients with mCRC underwent a metastatic biopsy for PDO establishment, before starting new systemic treatment. Predictors of PDO establishment were identified. PDOs were incubated with a seven-drug panel, including the patient's treatment, to determine drug sensitivity as measured by CyQUANT cell viability [area under the nonfitted "curve" of the raw viability or growth rate inhibition values (AUC and GRAUC) and concentration that gives half-maximal viability or GR inhibition (IC50 and GR50)]. Patient response was measured by size change of biopsied and all target lesions. The diagnostic performance was evaluated by positive predictive value, negative predictive value, and area under the ROC curve. Additionally, the association between PDO response and survival was assessed. RESULTS: A total of 232 patients were included, and 205 biopsies were obtained. PDO establishment success increased from 22% to 75%, yielding 52% overall. Male sex, increased lactate dehydrogenase, biopsy in academic hospitals, optimized culture conditions, and experience were related to PDO establishment success. In this interim analysis, focused on oxaliplatin-based doublet chemotherapy, 42 PDOs...