Human organoids: Fit for drug discovery?

Organoids are self-organizing three-dimensional (3D) in vitro tissues derived from pluripotent stem cells (PSCs) that recapitulate key structural and functional features of human organs. Their multicellular architecture and physiological relevance make them promising new approach methodologies (NAMs) for disease modeling, drug discovery, and toxicity testing. However, their reliability and scalability for compound screening remain under evaluation. This review summarizes current human PSC-derived organoid screening strategies, highlighting available readouts, related machine learning methods, and their potential advantages over traditional screening models. We also discuss major challenges, including assay robustness, throughput limitations, and the need for standardized protocols. Advancing validated and scalable approaches will be essential for integrating organoids into pharmaceutical development and improving the translational success of drug candidates.