P119 An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity

Introduction/BackgroundOvarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumour heterogeneity of OC are limited and hard to establish.MethodologyWe present a protocol that enables efficient derivat...

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Veröffentlicht in:International journal of gynecological cancer Jg. 29; H. Suppl 4; S. A132
Hauptverfasser: Kopper, O, de Witte, CJ, Lõhmussaar, K, Espejo Valle-Inclan, J, Hami, N, Kester, L, Balgobind, AV, Korving, J, Proost, N, Begthel, H, van Wijk, LM, Revilla, SA, Theeuwsen, R, van de Ven, M, van Roosmalen, MJ, Ponsioen, B, Ho, VWH, Neel, BG, Bosse, T, Gaarenstroom, KN, Vrieling, H, Vreeswijk, MPG, van Diest, PJ, Witteveen, PO, Jonges, T, Bos, JL, van Oudenaarden, A, Zweemer, RP, Snippert, HJG, Kloosterman, WP, Clevers, H
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Kidlington Elsevier Inc 01.11.2019
Elsevier Limited
Schlagworte:
Endometrial cancer
Ovarian cancer
ISSN:1048-891X, 1525-1438
Online-Zugang:Volltext
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Zusammenfassung:Introduction/BackgroundOvarian cancer (OC) is a heterogeneous disease usually diagnosed at a late stage. Experimental in vitro models that faithfully capture the hallmarks and tumour heterogeneity of OC are limited and hard to establish.MethodologyWe present a protocol that enables efficient derivation and long-term expansion of OC organoids.ResultsUtilizing 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 tumour 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.ConclusionTaken together, this demonstrates their potential application for research and personalized medicine.DisclosureNo competing interests. Applicable funding sources: EIF | Stand Up To Cancer (SU2C) [Clevers, Kopper, Balgobind, Begthel] KWF Kankerbestrijding (Dutch Cancer Society) - UU2015-7743 [de Witte, van Roosmalen, Witteveen, Zweemer, Kloosterman] Gieskes Strijbis Foundation (1816199) [Clevers, Witteveen, Kloosterman, Zweemer, Lõhmussaar, Espejo Valle-Inclan, Hami, Bos, Snippert] Published in Nature Medicine. April 2019. dx.doi.org/10.1038/s41591-019-0422-6.Abstract P119 Figure 1Ovarian cancer organoid biobankA. schematic of OC organoid. B. An overview of the number of established OC organoid lines according to their subtype distribution. MBT = Mucinous tumour, SBT = serous borderline tumour, CCC = clear cell carcinoma, END = endometrioid carcinoma, MC = mucinous carcinoma, LGS = low grade serous carcinoma, HGS = high grade serous carcinoma. C. In vitro drug sensitivity assay. Representative dose-response curves of HGS and LGS organoid lines treated with carboplatin/paclitaxel. Organoid line derived from recurrent disease (HGS-1-R3) shows acquired resistance. Dots represent the mean of technical duplicates. Error bars represent s.e.m. of technical duplicates.
Bibliographie:ObjectType-Article-1
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content type line 14
ISSN:1048-891X
1525-1438
DOI:10.1136/ijgc-2019-ESGO.182