Revolutionizing bladder cancer research: Harnessing 3D organoid technology to decode tumor heterogeneity and propel personalized therapeutics

Bladder cancer (BC), characterized by remarkable tumor heterogeneity, remains a challenging malignancy with limited therapeutic options. Emerging three-dimensional (3D) organoid models are transforming our understanding of BC biology by closely mimicking the complex tumor microenvironment (TME) and cellular interactions, far surpassing traditional two-dimensional (2D) cell culture systems. This review underscores the innovative advances in bladder cancer organoid technology, emphasizing their unique strengths in capturing intratumoral heterogeneity, enhancing drug sensitivity assessments, and facilitating personalized treatment approaches. We discuss diverse organoid systems, including spheroids, assembloids, and patient-derived organoid xenografts (PDOX), highlighting their exceptional ability to replicate individual patient tumor profiles. Furthermore, we explore integrated organoid-on-chip cultivation techniques incorporating 3D bioprinting and microfluidics, which notably improve precision, reproducibility, and scalability in organoid-based drug screening platforms. We advocate for optimized organoid cultivation protocols and synergistic integration with high-throughput analytical technologies, aiming ultimately to accelerate regimen breakthroughs in personalized medicine for bladder cancer patients.