Magdalena Skowronska, Ece Yıldız, Jens Grosch, Mairene Coto-Llerena
Patient-derived organoids (PDOs) have rapidly transitioned from research tools into promising platforms for clinical translation. In this review, we analyze 139 PDO-related clinical trials registered between 2023 and 2025 and contrast them with recent advances in disease modelling. Our analysis revealed a predominance of oncology-focused studies, with translational maturity spanning from foundational research to studies in which PDOs directly informed clinical decision-making. In contrast, non-oncology areas show extensive preclinical progress but remain trial-poor. We found that trial registration is geographically concentrated in a small number of countries, reflecting uneven global adoption. We then explored advances in disease modeling, mainly confined to preclinical studies, including immune-competent PDOs, complex organ-on-a-chip systems, synthetic matrices, AI-enabled platforms, and therapeutic transplantation. Based on these findings, we propose a conceptual framework outlining the trajectory of PDO adoption in clinical trials. This trajectory can be understood as three overlapping waves of translation: the first wave, focusing on oncology, has already demonstrated impacts on patient care; the second, targeting non-oncology diseases, is scientifically advanced but has not achieved widespread clinical application; and the third, involving frontier technologies, remains in the preclinical stage. Understanding these trajectories underscores the promise and challenges of PDOs that must be addressed for broader clinical adoption.