Abstract

3D organoids have emerged as a revolutionary tool in drug discovery, bridging the gap between traditional 2D cell cultures and complex in vivo systems with applications in the drug discovery field. This chapter explores the development and applications of organoids in drug discovery, highlighting their use in high-throughput screening assays and target identification and validation. We discuss key advancements in the establishment of organoids as a model system for high-throughput screening, and their implications for personalized medicine. Additionally, we examine the utility of organoids in cancer, to be used as a physiological relevant screening platform to model tumors for primary high-throughput screening campaign for drug discovery. By integrating organoids in the early drug development pipeline, researchers can reduce the reliance on using 2D transformed cell lines as screening tool and improve the efficiency and translational potential of new therapies. Ultimately, this chapter aims to illustrate the transformative role of 3D organoids in modern pharmacology and accelerating the discovery of novel therapeutics. © 2026 by World Scientific Publishing Co. Pte. Ltd. All rights reserved.