Patient-Derived Organoids Can Recapitulate Patient Responses in the Clinic

Comparison of organoid drug responses with how the patients with metastatic gastrointestinal cancers responded in the clinic

Cancer organoids are miniature, three-dimensional cell culture models that can be made from primary patient tumours and studied in the laboratory. Vlachogiannis et al. generated a live organoid biobank from patients with metastatic gastrointestinal cancers who have been enrolled in phase I or II clinical trials. In their study the patient-derived organoids had similar molecular profiles to those of the patient tumour, reinforcing their value as a platform for drug screening and development. The findings are published on 23 February 2018 in Science. 

The study team composed from researchers from The Institute of Cancer Research and Royal Marsden Hospital,both based in London,UK, University of Padua in Padua, Italy and Cancer Research UK Beatson Institute, Glasgow, UK wrote in study background that patient-derived organoids have recently emerged as robust preclinical models. However, their potential to predict clinical outcomes in patients has remained unclear. 

To allow to compare organoid drug responses with how the patient actually responded in the clinic, the study team had to generate living biobank of patient-derived organoids from metastatic, heavily pretreated patients with colorectal and gastroesophageal cancers recruited in phase I/II clinical trials. 

Phenotypic and genotypic profiling of patient-derived organoids showed a high degree of similarity to the original patient tumours. Molecular profiling of tumour organoids was matched to drug-screening results, suggesting that patient-derived organoids could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. 

The study team compared responses to anticancer agents ex vivo in organoids and patient-derived organoids-based orthotopic mouse tumour xenograft models with the responses of the patients in clinical trials. The data suggest that patient-derived organoids can recapitulate patient responses in the clinic. 

The authors concluded that such approach can be used to predict drug responses in the clinic and the patient-derived organoids could be implemented in precision medicine programmes. 

Reference

Vlachogiannis G, Hedayat S, Vatsiou A, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.Science 2018; 359(6378):920-926. DOI: 10.1126/science.aao2774