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

Oded Kopper, Chris J de Witte, Kadi Lõhmussaar, Jose Espejo Valle-Inclan, Nizar Hami, Lennart Kester, Anjali Vanita Balgobind, Jeroen Korving, Natalie Proost, Harry Begthel, Lise M van Wijk, Sonia Aristín Revilla, Rebecca Theeuwsen, Marieke van de Ven, Markus J van Roosmalen, Bas Ponsioen, Victor W H Ho, Benjamin G Neel, Tjalling Bosse, Katja N GaarenstroomHarry Vrieling, Maaike P G Vreeswijk, Paul J van Diest, Petronella O Witteveen, Trudy Jonges, Johannes L Bos, Alexander van Oudenaarden, Ronald P Zweemer, Hugo J G Snippert, Wigard P Kloosterman, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)838-849
Number of pages12
JournalNature Medicine
Volume25
Issue number5
DOIs
Publication statusPublished - May 2019

Keywords

  • Adult
  • Aged
  • Animals
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Female
  • Genomics
  • Heterografts
  • Humans
  • Mice, SCID
  • Middle Aged
  • Mutation
  • Organoids/pathology
  • Ovarian Neoplasms/drug therapy
  • Precision Medicine

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  • Cite this

    Kopper, O., de Witte, C. J., Lõhmussaar, K., Valle-Inclan, J. E., Hami, N., Kester, L., Balgobind, A. V., Korving, J., Proost, N., Begthel, H., van Wijk, L. M., Revilla, S. A., Theeuwsen, R., van de Ven, M., van Roosmalen, M. J., Ponsioen, B., Ho, V. W. H., Neel, B. G., Bosse, T., ... Clevers, H. (2019). An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nature Medicine, 25(5), 838-849. https://doi.org/10.1038/s41591-019-0422-6