Renal cell carcinoma organoids for precision medicine: bridging the gap between models and patients.

Renal cell carcinoma (RCC) poses significant challenges to precision oncology due to its pronounced molecular heterogeneity and complex tumor microenvironment (TME). Traditional two-dimensional (2D) cultures and animal models fall short in capturing patient-specific tumor biology, limiting their translational relevance. In contrast, three-dimensional (3D) organoid platforms offer structurally and functionally representative models that retain key pathological and pharmacological features of RCC. Notably, RCC organoids enable pharmacokinetic assessment, including drug penetration, metabolic activation, and off-target toxicity in a spatially organized context. This review outlines current strategies for RCC organoid construction-including patient-derived organoids (PDOs), air-liquid interface (ALI) cultures, scaffold-based matrices, and microfluidic systems-and evaluates their applications in drug screening, resistance modeling, and immunotherapy prediction. We further discuss technical and biological limitations such as phenotypic drift, inter-sample variability, and TME reconstruction, alongside emerging solutions in synthetic scaffolds, immune co-cultures, and multi-omics integration. In conclusion, RCC organoids are rapidly evolving into clinically actionable platforms, offering a scalable and predictive approach to personalized therapy in renal oncology.