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

高级别浆液性卵巢癌类器官的有效建立和药物反应分析平台

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作者:Wojciech Senkowski, Laura Gall-Mas, Matías Marín Falco, Yilin Li, Kari Lavikka, Mette C Kriegbaum, Jaana Oikkonen, Daria Bulanova, Elin J Pietras, Karolin Voßgröne, Yan-Jun Chen, Erdogan Pekcan Erkan, Jun Dai, Anastasia Lundgren, Mia Kristine Grønning Høg, Ida Marie Larsen, Tarja Lamminen, Katja Kai

Abstract

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.

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