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Cancer BiologybioRxiv

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

W. Senkowski, L. Gall-Mas, M. M. Falco, Y. Li, K. Lavikka, M. C. Kriegbaum, J. Oikkonen, D. Bulanova, E. J. Pietras, K. Vossgröne, Y.-J. Chen, E. P. Erkan, M. K. Gronning Hog, I. M. Larsen, T. Lamminen, K. Kaipio, J. Huvila, A. Virtanen, L. H. Engelholm, P. Christiansen, E. Santoni-Rugiu, K. Huhtinen, O. Carpen, J. Hynninen, S. Hautaniemi, , K. Wennerberg

Abstract

The broad research use of organoids from high-grade serous ovarian carcinoma (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 (55% 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 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 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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