Patient-derived organoids model treatment response of metastatic gastrointestinal cancers

Vlachogiannis, G. et al. (2018) Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science, 359(6378), pp. 920-926. (doi: 10.1126/science.aao2774) (PMID:29472484) (PMCID:PMC6112415)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Valeri, Dr Nicola and Sansom, Professor Owen and Braconi, Dr Chiara
• Authors: Vlachogiannis, G., Hedayat, S., Vatsiou, A., Jamin, Y., Fernández-Mateos, J., Khan, K., Lampis, A., Eason, K., Huntingford, I., Burke, R., Rata, M., Koh, D.-M., Tunariu, N., Collins, D., Hulkki-Wilson, S., Ragulan, C., Spiteri, I., Moorcraft, S. Y., Chau, I., Rao, S., Watkins, D., Fotiadis, N., Bali, M., Darvish-Damavandi, M., Lote, H., Eltahir, Z., Smyth, E. C., Begum, R., Clarke, P. A., Hahne, J. C., Dowsett, M., de Bono, J., Workman, P., Sadanandam, A., Fassan, M., Sansom, O. J., Eccles, S., Starling, N., Braconi, C., Sottoriva, A., Robinson, S. P., Cunningham, D., and Valeri, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Science
• Publisher: American Association for the Advancement of Science
• ISSN: 0036-8075
• ISSN (Online): 1095-9203
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Science 359(6378): 920-926
• Publisher Policy: Reproduced under a Creative Commons License