Patient-derived organoids model treatment response of metastatic gastrointestinal cancers
Top Cited Papers
- 23 February 2018
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 359 (6378), 920-926
- https://doi.org/10.1126/science.aao2774
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.Keywords
Funding Information
- FP7 People: Marie-Curie Actions (CIG334261)
- National Institute for Health Research (A62)
- Cancer Research UK (CEA A18052)
- European Commission (Marie Curie CIG 618154)
- European Research Council (331301)
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