Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses

Chris Jenske de Witte, Jose Espejo Valle-Inclan, Nizar Hami, Kadi Lõhmussaar, Oded Kopper, Celien Philomena Henrieke Vreuls, Geertruida Nellie Jonges, Paul van Diest, Luan Nguyen, Hans Clevers, Wigard Pieter Kloosterman, Edwin Cuppen, Hugo Johannes Gerhardus Snippert, Ronald Peter Zweemer, Petronella Oda Witteveen, Ellen Stelloo

Research output: Contribution to journal/periodicalArticleScientificpeer-review

124 Citations (Scopus)

Abstract

There remains an unmet need for preclinical models to enable personalized therapy for ovarian cancer (OC) patients. Here we evaluate the capacity of patient-derived organoids (PDOs) to predict clinical drug response and functional consequences of tumor heterogeneity. We included 36 whole-genome-characterized PDOs from 23 OC patients with known clinical histories. OC PDOs maintain the genomic features of the original tumor lesion and recapitulate patient response to neoadjuvant carboplatin/paclitaxel combination treatment. PDOs display inter- and intrapatient drug response heterogeneity to chemotherapy and targeted drugs, which can be partially explained by genetic aberrations. PDO drug screening identifies high responsiveness to at least one drug for 88% of patients. PDOs are valuable preclinical models that can provide insights into drug response for individual patients with OC, complementary to genetic testing. Generating PDOs of multiple tumor locations can improve clinical decision making and increase our knowledge of genetic and drug response heterogeneity.

Original languageEnglish
Pages (from-to)107762
JournalCell Reports
Volume31
Issue number11
DOIs
Publication statusPublished - 16 Jun 2020

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