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However, the lack of models with features consistent with human gallbladder tumours has hindered progress in pathogenic mechanisms and therapies.<\/jats:p><\/jats:sec>Methods<\/jats:title>We established organoid lines derived from human GBC as well as normal gallbladder and benign gallbladder adenoma (GBA) tissues. The histopathology signatures of organoid cultures were identified by H&E staining, immunohistochemistry and immunofluorescence. The genetic and transcriptional features of organoids were analysed by whole\u2010exome sequencing and RNA sequencing. A set of compounds targeting the most active signalling pathways in GBCs were screened for their ability to suppress GBC organoids. The antitumour effects of candidate compounds, CUDC\u2010101 and CUDC\u2010907, were evaluated in vitro and in vivo.<\/jats:p><\/jats:sec>Results<\/jats:title>The established organoids were cultured stably for more than 6 months and closely recapitulated the histopathology, genetic and transcriptional features, and intratumour heterogeneity of the primary tissues at the single\u2010cell level. Notably, expression profiling analysis of the organoids revealed a set of genes that varied across the three subtypes and thus may participate in the malignant progression of gallbladder diseases. More importantly, we found that the dual PI3K\/HDAC inhibitor CUDC\u2010907 significantly restrained the growth of various GBC organoids with minimal toxicity to normal gallbladder organoids.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Patient\u2010derived organoids are potentially a useful platform to explore molecular pathogenesis of gallbladder tumours and discover personalized drugs.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.678","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T03:40:28Z","timestamp":1643082028000},"source":"Crossref","is-referenced-by-count":80,"title":["Patient\u2010derived organoids for personalized gallbladder cancer modelling and drug screening"],"prefix":"10.1002","volume":"12","author":[{"given":"Bo","family":"Yuan","sequence":"first","affiliation":[{"name":"International Cooperation Laboratory on Signal Transduction Ministry of Education Key Laboratory on Signaling Regulation and Targeting Therapy of Liver Cancer 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