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原文摘要

Anti-cancer drug response prediction (DRP) is critically important for precision oncology and therapeutic development. Currently, most DRP models are developed using drug screening data from immortalized cancer cell lines, which can differ substantially from patient tumors at the genomic and molecular levels, even though patient tumor response is the ultimate prediction target. To help bridge this gap and bring DRP models closer to their intended clinical application, we conducted four drug screening studies using patient-derived organoids (PDOs), which more faithfully recapitulate patient tumors than immortalized cell lines. These studies generated data for improving and evaluating DRP models, including multi-omics profiles of PDO lines, drug feature data, and treatment response measurements. Using these data, we retrained and evaluated multiple publicly available DRP models under three model-building scenarios: training models using cell line data only, training models using combined cell line and PDO data, and pretraining models on cell line data followed by fine-tuning on PDO data. We then evaluated and compared model prediction performance on PDOs across these analysis scenarios. In addition, we also assessed the consistency of drug screening viability data generated by different laboratories using different assay technologies and/or experimental protocols.