摘要:SummarySelecting appropriate cell lines to represent a disease is crucial for the success of biomedical research, because the usage of less relevant cell lines could deliver misleading results. However, systematic guidance on cell line selection is unavailable. Here we developed a clinical Genomics-guided Prioritizing Strategy for Cancer Cell Lines (CCL-cGPS) and help to guide this process. Statistical analyses revealed CCL-cGPS selected cell lines were among the most appropriate models. Moreover, we observed a linear correlation between the drug response and CCL-cGPS score of cell lines for breast and thyroid cancers. Using RT4 cells selected by CCL-GPS, we identified mebendazole and digitoxin as candidate drugs against bladder cancer and validate their promising anticancer effect throughin vitroandin vivoexperiments. Additionally, a web tool was developed. In conclusion, CCL-cGPS bridges the gap between tumors and cell lines, presenting a helpful guide to select the most suitable cell line models.Graphical AbstractDisplay OmittedHighlights•Cell lines were ranked by the resemblance of transcriptional signatures to tumors•Among 44 tumor subtypes, CCL-cGPS provides proper cell lines for each subtype•CCL-cGPS was verified by the computational analysis,in vitroandin vivoassays•A web tool was developed to guide the selection of the most suitable cell linesCancer; Cancer Systems Biology; Genomics