Patient-derived prostate cancer organoids: model development, therapeutic applications, and challenges for precision oncology

Abstract

Prostate cancer ranks among the most prevalent male malignancies worldwide, with castration-resistant prostate cancer (CRPC) and drug resistance representing major clinical challenges. Conventional preclinical models fail to faithfully recapitulate tumor heterogeneity and the tumor microenvironment (TME). Patient-derived prostate cancer organoids (PCOs) represent a promising 3D model that largely preserves the genomic, phenotypic, and functional signatures of primary tumors. Building on prior studies that mostly focus on fragmented analyses and lack in-depth systematic integration, this narrative review attempts to establish a refined multidimensional research framework centered on “model optimization-mechanism exploration-clinical translation”. Notably, it underscores the unique advantages of engineered PCOs and heterotypic co-culture organoid systems in resolving key clinical bottlenecks, particularly lineage transformation-driven therapeutic resistance and patient-specific TME heterogeneity. This study systematically elaborates the establishment methodologies of PCOs, critically evaluates the strengths, limitations, and iterative optimization strategies of diverse culture systems, and summarizes the core applications of PCOs in exploring tumor cellular origin, capturing tumor heterogeneity, modeling TME interactions, screening drug sensitivity, investigating resistance mechanisms, and advancing precision medicine for prostate cancer. Although PCO-based platforms still possess inherent limitations, including low establishment efficiency, rigorous culture requirements, and incomplete TME reconstruction, they harbor substantial translational potential. Furthermore, this review proposes targeted optimization strategies based on bioengineering and synthetic biomaterials, prospects the clinical translation of standardized PCO systems, and discusses existing research contradictions and unaddressed gaps in this field, aiming to provide a comprehensive, critical and novel theoretical reference for further basic research and clinical application of PCOs in prostate cancer.