| Literature DB >> 31011202 |
Oded Kopper1,2, Chris J de Witte3, Kadi Lõhmussaar1,2, Jose Espejo Valle-Inclan3, Nizar Hami2,4, Lennart Kester1,2, Anjali Vanita Balgobind1,2, Jeroen Korving1,2, Natalie Proost5, Harry Begthel1,2, Lise M van Wijk6, Sonia Aristín Revilla1,2, Rebecca Theeuwsen5, Marieke van de Ven5, Markus J van Roosmalen3, Bas Ponsioen2,4, Victor W H Ho7, Benjamin G Neel7,8, Tjalling Bosse9, Katja N Gaarenstroom10, Harry Vrieling6, Maaike P G Vreeswijk6, Paul J van Diest11, Petronella O Witteveen12, Trudy Jonges11, Johannes L Bos2,4, Alexander van Oudenaarden1,2, Ronald P Zweemer13, Hugo J G Snippert2,4, Wigard P Kloosterman14, Hans Clevers15,16,17.
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.Entities:
Mesh：
Year: 2019 PMID： 31011202 DOI： 10.1038/s41591-019-0422-6
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440