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Abstract
The use of primary patient-derived organoids for drug sensitivity and resistance testing could play an important role in precision cancer medicine. We developed expandable ovarian cancer organoids in < 3 weeks; these organoids captured the characteristics of histological cancer subtypes and replicated the mutational landscape of the primary tumours. Seven pairs of organoids (3 high-grade serous, 1 clear cell, 3 endometrioid) and original tumours shared 59.5% (36.1–73.1%) of the variants identified. Copy number variations were also similar among organoids and primary tumours. The organoid that harboured the BRCA1 pathogenic variant (p.L63*) showed a higher sensitivity to PARP inhibitor, olaparib, as well as to platinum drugs compared to the other organoids, whereas an organoid derived from clear cell ovarian cancer was resistant to conventional drugs for ovarian cancer, namely platinum drugs, paclitaxel, and olaparib. The overall success rate of primary organoid culture, including those of various histological subtypes, was 80% (28/35). Our data show that patient-derived organoids are suitable physiological ex vivo cancer models that can be used to screen effective personalised ovarian cancer drugs.
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1 Keio University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); Keio University School of Medicine, JSR-Keio University Medical and Chemical Innovation Center (JKiC), Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959)
2 Keio University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); Keio University School of Medicine, JSR-Keio University Medical and Chemical Innovation Center (JKiC), Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); Okayama University, Department of Clinical Genomic Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan (GRID:grid.261356.5) (ISNI:0000 0001 1302 4472)
3 JSR Corp., JSR-Keio University Medical and Chemical Innovation Center (JKiC), Tokyo, Japan (GRID:grid.471148.f) (ISNI:0000 0004 0621 2661)
4 Keio University School of Medicine, JSR-Keio University Medical and Chemical Innovation Center (JKiC), Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); Keio University School of Medicine, Genomics Unit, Keio Cancer Center, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959)
5 Keio University School of Medicine, Department of Pathology, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); Showa University Northern Yokohama Hospital, Department of Pathology, Yokohama, Japan (GRID:grid.482675.a) (ISNI:0000 0004 1768 957X)
6 Keio University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959)
7 Keio University School of Medicine, Department of Obstetrics and Gynecology, Tokyo, Japan (GRID:grid.26091.3c) (ISNI:0000 0004 1936 9959); International University of Health and Welfare School of Medicine, Department of Obstetrics and Gynecology, Narita, Japan (GRID:grid.411731.1) (ISNI:0000 0004 0531 3030)