Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing

Yoshiko Nanki, Tatsuyuki Chiyoda, Akira Hirasawa, Aki Ookubo, Manabu Itoh, Masaru Ueno, Tomoko Akahane, Kaori Kameyama, Wataru Yamagami, Fumio Kataoka, Daisuke Aoki

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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.

Original languageEnglish
Article number12581
JournalScientific reports
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2020

ASJC Scopus subject areas

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    Nanki, Y., Chiyoda, T., Hirasawa, A., Ookubo, A., Itoh, M., Ueno, M., Akahane, T., Kameyama, K., Yamagami, W., Kataoka, F., & Aoki, D. (2020). Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing. Scientific reports, 10(1), [12581]. https://doi.org/10.1038/s41598-020-69488-9