A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids

The broad research use of organoids from high-grade serous ovarian cancer (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here, we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (53% vs. 23%–38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic, and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in a culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data are explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research. [Display omitted] •Protocol for establishment and long-term culture of HGSC organoids•Two culture medium formulations improve organoid establishment success rate•HGSC organoids retain genomic and phenotypic characteristics of original tumors•Culture medium impacts correlation of organoid drug responses with clinical outcomes Establishment of robust high-grade serous ovarian cancer (HGSC) organoid cultures has proven difficult. Senkowski et al. present a protocol for long-term culture of HGSC organoids from cryopreserved tissue at improved success rates, providing deep molecular model characterization and insights into correlating organoid drug responses with clinical outcomes.