Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

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.

Authors

Georgios Vlachogiannis; Somaieh Hedayat; Alexandra Vatsiou; Yann Jamin; Javier Fernández-Mateos; Khurum Khan; Andrea Lampis; Katherine Eason; Ian Said Huntingford; Rosemary Burke; Mihaela Rata; Dow‐Mu Koh; Nina Tunariu; David J. Collins; Sanna Hulkki-Wilson; Chanthirika Ragulan; Inmaculada Spiteri; Sing Yu Moorcraft; Ian Chau; Sheela Rao; David Watkins; Nicos Fotiadis; Maria Antonietta Bali; Mahnaz Darvish-Damavandi; Hazel Lote; Zakaria Eltahir; Elizabeth Smyth; Ruwaida Begum; Paul A. Clarke; Jens C. Hahne; Mitch Dowsett; Johann S. de Bono; Paul Workman; Anguraj Sadanandam; Matteo Fassan; Owen J. Sansom; Suzanne A. Eccles; Naureen Starling; Chiara Braconi; Andrea Sottoriva; Simon P. Robinson; David Cunningham; Nicola Valeri

Published

Feb 22, 2018

Journal or venue

Science

DOI

10.1126/science.aao2774

Paper type

journal article

Source

Openalex