Organoids in biliary tract cancers: Advances in modeling strategies and translational applications

Biliary organoids, as an emerging three-dimensional (3D) in vitro modeling technology, have demonstrated significant value in studying biliary development, elucidating disease mechanisms, drug screening, and enabling personalized medicine. This review provides a comprehensive overview of the current strategies for constructing biliary organoids, including their cellular sources, differentiation pathways, and functional characteristics. Particular emphasis is placed on their strengths and limitations in recapitulating biliary physiology, modeling biliary tract cancers (BTCs), and performing pharmacological and toxicological assessments. The article further analyzes major technical challenges, such as low modeling efficiency, limited structural and functional fidelity, absence of microenvironmental simulation, and issues of standardization and ethics. Future directions are proposed in the areas of multicellular co-culture systems, dynamic cultivation technologies, high-throughput platforms, and clinical translation pipelines. As a versatile and evolving tool, biliary organoids are poised to serve as a critical bridge between basic research and clinical applications, offering new insights and methodologies for the study and precision treatment of biliary tract cancers.