Cited by 1,973Cancer Cells and MetastasisBreast Cancer Treatment Studies3D Printing in Biomedical Research

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A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

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Sachs, Norman, de Ligt, Joep, Kopper, Oded, Gogola, Ewa, Bounova, Gergana, Weeber, Fleur, Balgobind, Anjali Vanita, Wind, Karin, Gracanin, Ana, Begthel, Harry, Korving, Jeroen, van Boxtel, Ruben, Duarte, Alexandra Alves, Lelieveld, Daphne, van Hoeck, Arne, Ernst, Robert Frans, Blokzijl, Francis, Nijman, Isaac Johannes, Hoogstraat, Marlous, van de Ven, Marieke, Egan, David Anthony, Zinzalla, Vittoria, Moll, Jurgen, Boj, Sylvia Fernandez, Voest, Emile Eugene, Wessels, Lodewyk, van Diest, Paul Joannes, Rottenberg, Sven, Vries, Robert Gerhardus Jacob, Cuppen, Edwin, Clevers, Hans·2018·Cell

DOI 10.1016/j.cell.2017.11.010

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Abstract

Breast cancer (BC) comprises multiple distinct subtypes that differ genetically, pathologically, and clinically. Here, we describe a robust protocol for long-term culturing of human mammary epithelial organoids. Using this protocol, >100 primary and metastatic BC organoid lines were generated, broadly recapitulating the diversity of the disease. BC organoid morphologies typically matched the histopathology, hormone receptor status, and HER2 status of the original tumor. DNA copy number variations as well as sequence changes were consistent within tumor-organoid pairs and largely retained even after extended passaging. BC organoids furthermore populated all major gene-expression-based classification groups and allowed in vitro drug screens that were consistent with in vivo xeno-transplantations and patient response. This study describes a representative collection of well-characterized BC organoids available for cancer research and drug development, as well as a strategy to assess in vitro drug response in a personalized fashion.

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Authors: Sachs, N., de Ligt, J., Kopper, O., Gogola, E., Bounova, G., Weeber, F., Balgobind, A. V., Wind, K., Gracanin, A., Begthel, H., Korving, J., van Boxtel, R., Duarte, A. A., Lelieveld, D., van Hoeck, A., Ernst, R. F., Blokzijl, F., Nijman, I. J., Hoogstraat, M., van de Ven, M., Egan, D. A., Zinzalla, V., Moll, J., Boj, S. F., Voest, E. E., Wessels, L., van Diest, P. J., Rottenberg, S., Vries, R. G. J., Cuppen, E., & Clevers, H.
Affiliations: Royal Netherlands Academy of Arts and Sciences (NL)
The Netherlands Cancer Institute (NL)
University Medical Center Utrecht (NL)
Utrecht University (NL)
Boehringer Ingelheim (Austria) (AT)
Oncode Institute (NL)
University of Bern (CH)
Corresponding author: Clevers, Hans
ORCID: Sachs, Norman
Gogola, Ewa
Weeber, Fleur
Begthel, Harry
Ernst, Robert Frans
Blokzijl, Francis
Hoogstraat, Marlous
Boj, Sylvia Fernandez
Voest, Emile Eugene
Wessels, Lodewyk
Rottenberg, Sven
Vries, Robert Gerhardus Jacob
Cuppen, Edwin
Clevers, Hans
Venue: Cell
Publisher: Elsevier BV
Published: 2018-01
Volume: 172
Issue: 1-2
Pages: 373-386.e10
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2017.11.010
OpenAlex: W2773981699
Cited by: 1,973
References: 79
Citations by year: 2026: 219 · 2025: 240 · 2024: 288 · 2023: 251 · 2022: 274 · 2021: 259 · 2020: 238 · 2019: 127 · 2018: 74
FWCI: 53.62
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 375 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
KNAW Research Portal (The Royal Netherlands Academy of Arts and Sciences) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Bern Open Repository and Information System (University of Bern) (submittedVersion)
Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (submittedVersion)
Utrecht University Repository (Utrecht University) (submittedVersion)
Funders: MKMD (114021012)
Netherlands Organization for Scientific Research (91615182, 114021012)
Stand Up to Cancer International Translational Cancer Research Grant
Stichting Vrienden van Hubrecht (2012.010)
Cancer Genomic Center (2014-186)
Boehringer-Ingelheim RCV GmbH & Co KG (141947)
Topics: Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords: breast cancer, organoid biobank, tumor heterogeneity, metastatic breast cancer, long-term organoid culture, copy number variation, gene expression subtypes, hormone receptor status, HER2 status, in vitro drug testing, xenotransplantation
MeSH terms: Animals, Antineoplastic Agents, Breast Neoplasms, Cells, Cultured, Drug Screening Assays, Antitumor, Female, Humans, Mice, Nude, Organoids, Tissue Banks, Genetic Heterogeneity, Mice, Precision Medicine

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A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity

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