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Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.


ABSTRACT: 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.

SUBMITTER: Vlachogiannis G 

PROVIDER: S-EPMC6112415 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.

Vlachogiannis Georgios G   Hedayat Somaieh S   Vatsiou Alexandra A   Jamin Yann Y   Fernández-Mateos Javier J   Khan Khurum K   Lampis Andrea A   Eason Katherine K   Huntingford Ian I   Burke Rosemary R   Rata Mihaela M   Koh Dow-Mu DM   Tunariu Nina N   Collins David D   Hulkki-Wilson Sanna S   Ragulan Chanthirika C   Spiteri Inmaculada I   Moorcraft Sing Yu SY   Chau Ian I   Rao Sheela S   Watkins David D   Fotiadis Nicos N   Bali Maria M   Darvish-Damavandi Mahnaz M   Lote Hazel H   Eltahir Zakaria Z   Smyth Elizabeth C EC   Begum Ruwaida R   Clarke Paul A PA   Hahne Jens C JC   Dowsett Mitchell M   de Bono Johann J   Workman Paul P   Sadanandam Anguraj A   Fassan Matteo M   Sansom Owen J OJ   Eccles Suzanne S   Starling Naureen N   Braconi Chiara C   Sottoriva Andrea A   Robinson Simon P SP   Cunningham David D   Valeri Nicola N  

Science (New York, N.Y.) 20180201 6378


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 d  ...[more]

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