Patient-derived organoids in renal cell carcinoma: A review of methodologies and applications

Renal cell carcinoma (RCC) is a heterogeneous malignancy marked by considerable variability in tumor biology and treatment response. Traditional 2-dimensional (2D) cell culture models have provided valuable insights into RCC, but their limitations in replicating the tumor microenvironment and complex cellular interactions necessitate more advanced platforms. Three-dimensional (3D) culture systems - particularly patient-derived organoids (PDOs) - have emerged as promising tools to model RCC with enhanced physiological relevance. This review provides a comprehensive overview of current methodologies for generating RCC PDOs, including Matrigel-based cultures, air-liquid interface (ALI) systems, and microfluidic organ-on-a-chip technologies. We explore the critical factors influencing successful organoid development, such as tissue sourcing, culture media composition, and the incorporation of tumor microenvironment components. The applications of RCC PDOs span drug screening, modeling tumorigenesis and metastasis, immunotherapy studies, and basic research into RCC biology. Notably, organoids have shown potential for predicting individual patient responses to therapy, advancing the vision of personalized medicine. Despite their promise, challenges remain in terms of long-term culture stability, standardization of protocols, and comprehensive microenvironment replication. Future directions include refining bioengineering techniques, integrating multi-omics analyses, and enhancing immunocompetency in organoid systems. In conclusion, RCC PDOs represent a transformative advance in preclinical modeling, with growing utility in translational and precision oncology.