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

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ID: 108474
2020
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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.
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de-witte2020patientderivedcell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors de Witte, Chris Jenske;Espejo Valle-Inclan, Jose;Hami, Nizar;Lõhmussaar, Kadi;Kopper, Oded;Vreuls, Celien Philomena Henrieke;Jonges, Geertruida Nellie;van Diest, Paul;Nguyen, Luan;Clevers, Hans;Kloosterman, Wigard Pieter;Cuppen, Edwin;Snippert, Hugo Johannes Gerhardus;Zweemer, Ronald Peter;Witteveen, Petronella Oda;Stelloo, Ellen;
Journal Cell reports
Year 2020
DOI
S2211-1247(20)30742-7
URL
Keywords
Chemotherapy ovarian cancer heterogeneity wgs drug screening organoids clinical response

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