Developing Organoids from Ovarian Cancer as Experimental and Preclinical Models
Open accessAbstract
Ovarian cancer (OC) represents the most dismal gynecological cancer. Pathobiology is poorly understood, mainly due to lack of appropriate study models. Organoids, defined as self-developing three-dimensional in vitro reconstructions of tissues, provide powerful tools to model human diseases. Here, we established organoid cultures from patient-derived OC, in particular from the most prevalent high-grade serous OC (HGSOC). Testing multiple culture medium components identified neuregulin-1 (NRG1) as key factor in maximizing OC organoid development and growth, although overall derivation efficiency remained moderate (36% for HGSOC patients, 44% for all patients together). Established organoid lines showed patient tumor-dependent morphology and disease characteristics, and recapitulated the parent tumor's marker expression and mutational landscape. Moreover, the organoids displayed tumor-specific sensitivity to clinical HGSOC chemotherapeutic drugs. Patient-derived OC organoids provide powerful tools for the study of the cancer's pathobiology (such as importance of the NRG1/ERBB pathway) as well as advanced preclinical tools for (personalized) drug screening and discovery.
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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 Maenhoudt et al., 2020
Addition of neuregulin-1 (NRG1) to culture medium can increase the proliferation time of primary organoid cultures from fresh and cryopreserved HGSOC and LGSOC, particularly in slower-growing cultures.
“Work by Maenhoudt and colleagues identified that the addition of neuregulin-1 (NRG1) to culture medium can increase the proliferation time of primary organoid cultures from fresh and cryopreserved HGSOC and LGSOC, particularly in slower-growing cultures (Maenhoudt 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 Maenhoudt et al., 2020
Numerous studies have shown the utility of ovarian cancer organoids of various histotypes for drug screening, with maintenance of mutational profiles and accurate reproduction of treatment responses when challenged with FDA-approved clinically utilized drugs.
“Further, numerous studies have shown the utility of ovarian cancer organoids of various histotypes for drug screening, with maintenance of mutational profiles and accurate reproduction of treatment responses when challenged with FDA-approved clinically utilized drugs (Kopper et al., 2019; Maenhoudt et al., 2020; 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 Maenhoudt et al., 2020
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References 58 · Cited by 186
- Authors
- Maenhoudt, N., Defraye, C., Boretto, M., Jan, Z., Heremans, R., Boeckx, B., Hermans, F., Arijs, I., Cox, B., Van Nieuwenhuysen, E., Vergote, I., Van Rompuy, A.-S., Lambrechts, D., Timmerman, D., & Vankelecom, H.
- Affiliations
- KU Leuven (BE)
- Universitair Ziekenhuis Leuven (BE)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Hasselt University (BE)
- Corresponding author
- Vankelecom, Hugo
- ORCID
- Venue
- Stem Cell Reports
- Publisher
- Elsevier BV
- Published
- 2020-04
- Volume
- 14
- Issue
- 4
- Pages
- 717-729
- ISSN
- 2213-6711 (ISSN-L)
- PMC
- PMC7160357
- OpenAlex
- W3014845361
- Cited by
- 186
- References
- 58
- Citations by year
- 2026: 18 · 2025: 35 · 2024: 32 · 2023: 35 · 2022: 30 · 2021: 29 · 2020: 7
- FWCI
- 22.23
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Stem Cell Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lirias (KU Leuven) (submittedVersion, other-oa)
- Document Server@UHasselt (UHasselt) (submittedVersion, cc-by-nc-nd)
- Funders
- Fonds Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
- Keywords
- ovarian cancer, organoids, high-grade serous ovarian cancer, patient-derived organoids, neuregulin-1, ErbB signaling, culture medium optimization, tumor mutational landscape, chemosensitivity, drug screening, preclinical models
- MeSH terms
- Antineoplastic Agents, Female, Humans, Models, Biological, Organ Culture Techniques, Organoids, Ovarian Neoplasms, Neuregulin-1
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