Journal article
BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance.
- Duarte AA Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Gogola E Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Sachs N Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, Utrecht, The Netherlands.
- Barazas M Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Annunziato S Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- R de Ruiter J Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Velds A Genomics Core Facility, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Blatter S Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
- Houthuijzen JM Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- van de Ven M Mouse Clinic for Cancer and Aging (MCCA), Preclinical Intervention Unit, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Clevers H Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Centre Utrecht, Utrecht, The Netherlands.
- Borst P Division of Molecular Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands.
- Jonkers J Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- Rottenberg S Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
- 2017-12-20
Published in:
- Nature methods. - 2018
ATP Binding Cassette Transporter, Subfamily B
Animals
Antineoplastic Agents
BRCA1 Protein
BRCA2 Protein
Cell Proliferation
Drug Resistance, Neoplasm
Female
Mammary Neoplasms, Animal
Mice
Mice, Knockout
Organ Culture Techniques
Organoids
Poly(ADP-ribose) Polymerase Inhibitors
Tumor Suppressor Proteins
English
Poly(ADP-ribose) polymerase inhibition (PARPi) is a promising new therapeutic approach for the treatment of cancers that show homologous recombination deficiency (HRD). Despite the success of PARPi in targeting HRD in tumors that lack the tumor suppressor function of BRCA1 or BRCA2, drug resistance poses a major obstacle. We developed three-dimensional cancer organoids derived from genetically engineered mouse models (GEMMs) for BRCA1- and BRCA2-deficient cancers. Unlike conventional cell lines or mammospheres, organoid cultures can be efficiently derived and rapidly expanded in vitro. Orthotopically transplanted organoids give rise to mammary tumors that recapitulate the epithelial morphology and preserve the drug response of the original tumor. Notably, GEMM-tumor-derived organoids can be easily genetically modified, making them a powerful tool for genetic studies of tumor biology and drug resistance.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1038/nmeth.4535
- PMID 29256493
- Persistent URL
- https://sonar.ch/global/documents/279013
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