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

doi:10.1016/j.celrep.2020.107762

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

Hubrecht Institute

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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.

Originele taal-2	Engels
Pagina's (van-tot)	107762
Tijdschrift	Cell Reports
Volume	31
Nummer van het tijdschrift	11
DOI's	https://doi.org/10.1016/j.celrep.2020.107762
Status	Gepubliceerd - 16 jun. 2020

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10.1016/j.celrep.2020.107762

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de Witte, C. J., Espejo Valle-Inclan, J., Hami, N., Lõhmussaar, K., Kopper, O., Vreuls, C. P. H., Jonges, G. N., van Diest, P., Nguyen, L., Clevers, H., Kloosterman, W. P., Cuppen, E., Snippert, H. J. G., Zweemer, R. P., Witteveen, P. O., & Stelloo, E. (2020). Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses. Cell Reports, 31(11), 107762. https://doi.org/10.1016/j.celrep.2020.107762

@article{4108a9d93056417b84e1b29acf44532a,

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

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.",

author = "{de Witte}, {Chris Jenske} and {Espejo Valle-Inclan}, Jose and Nizar Hami and Kadi L{\~o}hmussaar and Oded Kopper and Vreuls, {Celien Philomena Henrieke} and Jonges, {Geertruida Nellie} and {van Diest}, Paul and Luan Nguyen and Hans Clevers and Kloosterman, {Wigard Pieter} and Edwin Cuppen and Snippert, {Hugo Johannes Gerhardus} and Zweemer, {Ronald Peter} and Witteveen, {Petronella Oda} and Ellen Stelloo",

year = "2020",

month = jun,

day = "16",

doi = "10.1016/j.celrep.2020.107762",

language = "English",

volume = "31",

pages = "107762",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "11",

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de Witte, CJ, Espejo Valle-Inclan, J, Hami, N, Lõhmussaar, K, Kopper, O, Vreuls, CPH, Jonges, GN, van Diest, P, Nguyen, L, Clevers, H, Kloosterman, WP, Cuppen, E, Snippert, HJG, Zweemer, RP, Witteveen, PO & Stelloo, E 2020, 'Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses', Cell Reports, vol. 31, nr. 11, blz. 107762. https://doi.org/10.1016/j.celrep.2020.107762

Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses. / de Witte, Chris Jenske; Espejo Valle-Inclan, Jose; Hami, Nizar et al.
In: Cell Reports, Vol. 31, Nr. 11, 16.06.2020, blz. 107762.

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgave › Artikel › Wetenschappelijk › peer review

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T1 - Patient-Derived Ovarian Cancer Organoids Mimic Clinical Response and Exhibit Heterogeneous Inter- and Intrapatient Drug Responses

AU - de Witte, Chris Jenske

AU - Espejo Valle-Inclan, Jose

AU - Hami, Nizar

AU - Lõhmussaar, Kadi

AU - Kopper, Oded

AU - Vreuls, Celien Philomena Henrieke

AU - Jonges, Geertruida Nellie

AU - van Diest, Paul

AU - Nguyen, Luan

AU - Clevers, Hans

AU - Kloosterman, Wigard Pieter

AU - Cuppen, Edwin

AU - Snippert, Hugo Johannes Gerhardus

AU - Zweemer, Ronald Peter

AU - Witteveen, Petronella Oda

AU - Stelloo, Ellen

PY - 2020/6/16

Y1 - 2020/6/16

N2 - 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.

AB - 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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DO - 10.1016/j.celrep.2020.107762

M3 - Article

C2 - 32553164

SN - 2211-1247

VL - 31

SP - 107762

JO - Cell Reports

JF - Cell Reports

IS - 11

ER -

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

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