Emerging Role of Human Organoids in Drug Discovery and Development: Current Advances and Challenges

Abstract

Human tissue-derived organoid technologies have emerged as advanced platforms for drug discovery and development by providing physiologically relevant alternatives to conventional 2D cell cultures and animal
models. Organoids closely mimic the structural, genetic, and functional characteristics of native organs, enabling improved investigation of disease mechanisms, drug responses, and toxicity. This review summarizes
recent advances in organoid technology derived from pluripotent and adult stem cells for pharmaceutical and biomedical applications. Studies involving cancer, neurodegenerative, infectious, and rare genetic disease models were analyzed with emphasis on drug screening, personalized medicine, and translational research applications. Organoids demonstrated superior physiological relevance and improved prediction of pharmacodynamic and pharmacokinetic responses compared with traditional models. Patient-derived tumor organoids showed strong predictive accuracy for chemotherapy and immunotherapy outcomes. Organoids also enabled investigation of disease progression and individualized treatment responses. Despite significant progress, limitations including lack of vascularization, absence of immune and stromal interactions, batch variability, scalability challenges,
and ethical concerns remain barriers to clinical translation. Continued development of standardized culture systems and multicellular organoid platforms may improve reproducibility and regulatory acceptance. Overall, organoid technology represents a promising approach for precision medicine, personalized therapy, and next- generation drug development.