A platform for efficient establishment and drug-response profiling of high-grade serous ovarian cancer organoids
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, Erdoğan Pekcan Erkan, Jun Dai, Anastasia Lundgren, Mia Kristine Grønning Høg, Ida Marie Larsen, Tarja Lamminen, Katja Kaipio, Jutta Huvila, Anni Virtanen, Lars H. Engelholm, P. Christiansen, Eric Santoni‐Rugiu, Kaisa Huhtinen, Olli Carpén, Johanna Hynninen, Sampsa Hautaniemi, Anna Vähärautio, Krister Wennerberg
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.