Emerging organoids and organoids-on-chip platforms for translational development of antibody‒drug conjugates and next-generation bioconjugates

The rapid evolution of antibody‒drug conjugates (ADCs) and emerging X-drug conjugates (XDCs) has revolutionized targeted cancer therapy, yet their clinical translation is severely bottlenecked by the lack of human-relevant preclinical models. To bridge this translational gap, patient-derived organoids and organoids-on-chip (OoC) platforms recapitulate key features of human tumor biology, offering powerful tools for investigating cancer heterogeneity and improving the predictive evaluation of bioconjugated therapeutics. In this review, we systematically summarize the current landscape and challenges of ADCs and XDCs development across existing preclinical models, critically discuss the concepts, biological principles and application potential of organoid- and OoC-based systems, and highlight recent global policy developments and collaborative initiatives shaping their translational implementation. Finally, we highlight key challenges and future perspectives for leveraging organoids and OoCs in the druggability assessment, optimization, and translational development of ADCs and XDCs.