Bridging the validation gap: organoids as functional decision systems in drug repurposing

作者：Gulisano M · 发表于：Pharmacological research · 年份：2026 · DOI：10.1016/j.phrs.2026.108360 · 研究领域：Artificial intelligence、Drug repurposing、In silico、New Approach Methodologies、Organoids、Rare diseases、Translational pharmacology

Drug repurposing offers a faster and less costly route to therapeutic development, yet its translational success remains constrained by a critical scientific and evidentiary gap: the absence of human-relevant intermediate validation systems capable of converting computationally generated candidates into biologically grounded, clinically actionable evidence. In this opinion paper, we propose that human organoid platforms-particularly when integrated with artificial intelligence (AI)-driven candidate prioritisation upstream and multidimensional data analytics downstream-can function as context-specific, fit-for-purpose functional decision layers within repurposing pipelines-decision-grade within a defined context of use rather than possessing it as a generalisable property of the platform. We outline a hybrid framework coupling in silico discovery, organoid-based functional validation, and AI-enabled response interpretation, and we propose the disease categories in which this approach is most immediately applicable. We further discuss current operational challenges alongside their enabling solutions, and contextualise the framework within the evolving regulatory landscapes of the FDA and EMA as both agencies advance the integration of New Approach Methodologies (NAMs).