Organoid-Based Drug Screening Platforms

Abstract

Organoid-based drug screening platforms culture miniature, self-organising tissue structures from patient-derived or stem cells and expose them to candidate compounds, bridging the gap between two-dimensional cell-line assays and animal models, yet their integration into pharmaceutical discovery pipelines remains inconsistent across tumour types and therapeutic areas. We evaluated 222 organoid drug screening programmes conducted across pharmaceutical and academic centres in Estonia and Spain between 2015 and 2024, spanning five organoid categories: colorectal tumour organoids, pancreatic ductal adenocarcinoma organoids, breast cancer organoids, liver and hepatobiliary organoids, and lung cancer organoids. An Organoid Drug Screening Maturity Index (ODSMI) was constructed from five sub-scores - drug response prediction accuracy, throughput scalability, patient-to-organoid concordance, assay reproducibility, and integration into clinical decision-making -- with weights from regression against sustained adoption into active drug discovery or clinical pharmacotyping workflows. ODSMI correlated with adoption at r = +0.84 and discriminated adopted from discontinued platforms with an AUC of 0.884. Colorectal organoid platforms scored highest (mean ODSMI 0.824), while lung cancer organoids trailed at 0.598. Only 35.6 percent of programmes exceeded the 0.75 threshold. Drug response prediction accuracy carried the largest regression weight (beta = +0.278), followed by patient-to-organoid concordance (beta = +0.230).