Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
de Bono, J
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Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.
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Drug Resistance, Neoplasm
Xenograft Model Antitumor Assays
Signal Transduction & Molecular Pharmacology
Gastrointestinal Cancers Clinical Trials
Medicine (RMH Smith Cunningham)
Prostate Cancer Targeted Therapy Group
Evolutionary Genomics & Modelling
Gastrointestinal Cancer Biology and Genomics
Systems and Precision Cancer Medicine
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Science, 359 (6378), pp. 920 - 926