TY - JOUR
T1 - Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing
AU - Nanki, Yoshiko
AU - Chiyoda, Tatsuyuki
AU - Hirasawa, Akira
AU - Ookubo, Aki
AU - Itoh, Manabu
AU - Ueno, Masaru
AU - Akahane, Tomoko
AU - Kameyama, Kaori
AU - Yamagami, Wataru
AU - Kataoka, Fumio
AU - Aoki, Daisuke
N1 - Funding Information:
This research was supported by JSPS Bilateral program, JSPS KAKENHI Grant Numbers: 17K19611, 17K19613, 18K09298, and 19K18651. This work was also supported by JSR Corporation as a JKiC Strategic Project. The authors thank Ms. Tomomi Noda, Ms. Atsuko Fukushima for their biobank and data management, and Ms. Keiko Abe and Ms. Shihomi Yamaguchi for secretarial assistance. The authors also thank colleagues at the Department of Obstetrics and Gynecology Keio University School of Medicine for sample collection.
Funding Information:
A.O., M.I., and M.U. are employees of JSR Corporation. Y.N., T.C., A.H., and T.A. report receiving a research grant from JSR Corporation. Other authors declare no conflict of interest regarding this manuscript.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - 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.
AB - 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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U2 - 10.1038/s41598-020-69488-9
DO - 10.1038/s41598-020-69488-9
M3 - Article
C2 - 32724113
AN - SCOPUS:85088646884
SN - 2045-2322
VL - 10
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 12581
ER -
