In an article published on 22 April 2019 in the Nature Medicine, a group of Dutch investigators led by Wigard P. Kloosterman of the Centre for Molecular Medicine, University Medical Centre (UMC) Utrecht and Hans Clevers of the Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and UMC Utrecht, Utrecht, the Netherlands report findings from established biobank of ovarian cancer organoids which recapitulate the histopathological and molecular hallmarks of patient tumours and provides a resource for preclinical research.
Ovarian cancer is a heterogeneous disease usually diagnosed in advanced stage. Experimental in vitro models that capture the hallmarks and tumour heterogeneity of ovarian cancer are limited and hard to establish, the authors wrote in study background.
The study investigators established a protocol that enables efficient derivation and long-term expansion of ovarian cancer organoids. By utilising the protocol, they have established 56 organoid lines from 32 patients, representing all main subtypes of ovarian cancer.
The study team found that ovarian cancer organoids recapitulate histological and genomic features of the pertinent lesion from which they were derived, and therefore illustrate intra- and interpatient heterogeneity. They can be also genetically modified.
Furthermore, the researchers showed that ovarian cancer organoids can be used for drug-screening assays. They capture different tumour subtype responses to the standard platinum-based chemotherapy, including acquired resistance to chemotherapy in recurrent setting. Finally, ovarian cancer organoids can be xenografted, enabling in vivo drug-sensitivity assays.
These findings led the study team to conclude that ovarian cancer organoids show potential application for research and personalised medicine.
The authors acknowledged a work of number of colleagues who helped their work in different domains, such as providing support of ethical regulatory affairs, supplying clinical data, help with DNA isolations, help with culturing organoids, and the Utrecht Platform for Organoid Technology at UMC Utrecht for patient inclusion and tissue acquisition. The Preclinical Intervention Unit of the Mouse Clinic for Cancer and Ageing at the NKI performed the intervention studies. The first author received support from Marie Skłodowska-Curie IF grant. This work was funded by the gravitation programme CancerGenomiCs.nl and grant from the Netherlands Organisation for Scientific Research, Stand Up to Cancer International Translational Cancer Research Grant, a programme of the Entertainment Industry Foundation administered by the AACR, Dutch Cancer Society grants, and a grant from the Gieskes Strijbis Foundation.
Reference
Kopper O, de Witte CJ, Lõhmussaar K, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nature Medicine; Published online 22 April 2019.