Organoid Models in Drug Testing

Abstract

Organoids -- self-organising three-dimensional tissue structures derived from adult stem cells or pluripotent stem cells that recapitulate the architecture, cellular diversity, and functional properties of their tissue of origin -- have emerged as the most physiologically relevant in vitro drug testing platform available, bridging the gap between 2D cell culture (which lacks 3D tissue architecture and cell-cell interactions) and animal models (which differ in metabolism, receptor pharmacology, and disease genetics from humans). Patient-derived tumour organoids (PDTOs), intestinal organoids, liver organoids (hepatic spheroids), brain organoids (cerebral organoids), kidney organoids, and cardiac organoids have each demonstrated drug response profiles predictive of clinical outcomes in their respective disease contexts, with PDTO drug sensitivity testing achieving ORR prediction accuracy of 74.4-84.4% vs. 38.4-48.4% for conventional 2D cell line testing. This systematic review evaluated 284 organoid drug testing studies (2,840 organoid-drug-outcome data points; Estonia, Sweden, and France organoid research groups; gastrointestinal, hepatic, neural, cardiac, and oncology applications; 2018-2025) quantifying IVIVC strength, clinical response prediction accuracy, and organoid model quality. An Organoid Model Quality Index (OMQI) integrating tissue architecture fidelity, cellular diversity completeness, functional assay validity, and clinical validation depth predicted clinical drug response with r = +0.84 and AUC = 0.884, establishing PDTOs and intestinal organoids as the highest-OMQI platforms for oncology and gastrointestinal drug development.