Patient-derived Ovarian Cancer Organoids Capture the Genomic Profiles of Primary Tumours Applicable for Drug Sensitivity and Resistance Testing
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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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These ovarian tumoroid models show great promise for conducting ex vivo drug assays to predict therapeutic response in the women from which they were established.
“These models show great promise for conducting ex vivo drug assays to predict therapeutic response in the women from which they were established (De Witte et al., 2020; Maenhoudt et al., 2020; Nanki et al., 2020; Gorski et al., 2021).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Nanki et al., 2020
Nanki and colleagues propagated primary ovarian tumor organoids from a variety of histological subtypes including HGSOC, OCCC, and EnOC with an 80% success rate and maintenance of their original tumor mutational profiles.
“Nanki and colleagues were able to propagate primary ovarian tumor organoids from a variety of histological subtypes including HGSOC, OCCC, and EnOC with an 80% success rate and maintenance of their original tumor mutational profiles (Nanki et al., 2020).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Nanki et al., 2020
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- Authors
- Nanki, Y., Chiyoda, T., Hirasawa, A., Ookubo, A., Itoh, M., Ueno, M., Akahane, T., Kameyama, K., Yamagami, W., Kataoka, F., & Aoki, D.
- Affiliations
- Keio University (JP)
- Okayama University (JP)
- Corresponding author
- Chiyoda, Tatsuyuki
- Hirasawa, Akira
- ORCID
- Venue
- Scientific Reports
- Published
- 2020-07-28
- Volume
- 10
- Issue
- 1
- Pages
- 12581-12581
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC7387538
- OpenAlex
- W3045560651
- Cited by
- 165
- References
- 34
- Citations by year
- 2026: 23 · 2025: 25 · 2024: 33 · 2023: 29 · 2022: 29 · 2021: 23 · 2020: 3
- FWCI
- 18.52
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- KeiO Associated Repository of Academic Resources (Keio University) (submittedVersion)
- Okayama University Scientific Achievement Repository (Okayama University) (submittedVersion)
- Funders
- JSPS Bilateral program
- JSR Corporation (JKiC Strategic Project)
- JSPS KAKENHI (17K19611, 17K19613, 18K09298, 19K18651)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- ovarian cancer, patient-derived organoids, drug susceptibility testing, drug resistance, mutational landscape, copy number variation, high-grade serous ovarian cancer, ovarian clear cell carcinoma, endometrioid ovarian cancer, BRCA1 pathogenic variants, PARP inhibitors, olaparib, platinum drugs, paclitaxel, precision oncology
- MeSH terms
- Antineoplastic Agents, Female, Humans, Organoids, Ovarian Neoplasms, Genome, Human, Drug Resistance, Neoplasm, Precision Medicine
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