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Nat Med. 2019 May;25(5):838-849. doi: 10.1038/s41591-019-0422-6. Epub 2019 Apr 22.

An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity.

Author information

1
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, the Netherlands.
2
Oncode Institute, Utrecht, the Netherlands.
3
Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
4
Molecular Cancer Research, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
5
Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing (MCCA) at the NKI, Amsterdam, the Netherlands.
6
Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands.
7
Princess Margaret Cancer Center, University Health Network, Toronto, Ontario, Canada.
8
Perlmutter Cancer Center, NYU Langone Health, New York, NY, USA.
9
Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands.
10
Department of Gynecology, Leiden University Medical Center, Leiden, the Netherlands.
11
Department of Pathology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
12
Department of Medical Oncology, Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
13
Department of Gynaecological Oncology, Cancer Center, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
14
Center for Molecular Medicine, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands. w.kloosterman@umcutrecht.nl.
15
Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, the Netherlands. h.clevers@hubrecht.eu.
16
Oncode Institute, Utrecht, the Netherlands. h.clevers@hubrecht.eu.
17
The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. h.clevers@hubrecht.eu.

Abstract

Ovarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of OC are limited and hard to establish. We present a protocol that enables efficient derivation and long-term expansion of OC organoids. Utilizing this protocol, we have established 56 organoid lines from 32 patients, representing all main subtypes of OC. OC organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, illustrating intra- and interpatient heterogeneity, and can be genetically modified. We show that OC organoids can be used for drug-screening assays and capture different tumor subtype responses to the gold standard platinum-based chemotherapy, including acquisition of chemoresistance in recurrent disease. Finally, OC organoids can be xenografted, enabling in vivo drug-sensitivity assays. Taken together, this demonstrates their potential application for research and personalized medicine.

PMID:
31011202
DOI:
10.1038/s41591-019-0422-6
[Indexed for MEDLINE]

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