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 |
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01.11.2019
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| Abstract | 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. |
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| AbstractList | 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.[Figure omitted. See PDF] 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. |
| Author | Kopper, O Theeuwsen, R Korving, J Ponsioen, B van Diest, PJ Bosse, T Ho, VWH Gaarenstroom, KN Clevers, H Jonges, T van Oudenaarden, A Balgobind, AV Kester, L Witteveen, PO Vrieling, H Espejo Valle-Inclan, J Snippert, HJG Revilla, SA Begthel, H Proost, N Neel, BG Lõhmussaar, K van Wijk, LM Kloosterman, WP Hami, N Bos, JL Zweemer, RP de Witte, CJ Vreeswijk, MPG van Roosmalen, MJ van de Ven, M |
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The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 19 givenname: T surname: Bosse fullname: Bosse, T organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 20 givenname: KN surname: Gaarenstroom fullname: Gaarenstroom, KN organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 21 givenname: H surname: Vrieling fullname: Vrieling, H organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 22 givenname: MPG surname: Vreeswijk fullname: Vreeswijk, MPG organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 23 givenname: PJ surname: van Diest fullname: van Diest, PJ organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 24 givenname: PO surname: Witteveen fullname: Witteveen, PO organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 25 givenname: T surname: Jonges fullname: Jonges, T organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 26 givenname: JL surname: Bos fullname: Bos, JL organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 27 givenname: A surname: van Oudenaarden fullname: van Oudenaarden, A organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 28 givenname: RP surname: Zweemer fullname: Zweemer, RP organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 29 givenname: HJG surname: Snippert fullname: Snippert, HJG organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 30 givenname: WP surname: Kloosterman fullname: Kloosterman, WP organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands – sequence: 31 givenname: H surname: Clevers fullname: Clevers, H organization: The Netherlands Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands |
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| Title | P119 An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity |
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