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Updated: Feb 16, 2026
Growth and Characterization of Irradiated Organoids from Mammary Glands
Published on: May 3, 2019
BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance
Alexandra A Duarte1, Ewa Gogola1, Norman Sachs2
1Division of Molecular Pathology and Cancer Genomics Netherlands, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract:
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.
Insights
Poly(ADP-ribose) polymerase inhibition (PARPi) offers a new cancer therapy for homologous recombination deficiency (HRD). Researchers created 3D organoids from mouse models to study PARPi resistance in BRCA1/2-deficient cancers.
Area of Science:
- Oncology
- Genetics
- Biotechnology
Background:
- Poly(ADP-ribose) polymerase inhibition (PARPi) is a key therapy for cancers with homologous recombination deficiency (HRD).
- Drug resistance limits PARPi efficacy in BRCA1/2-deficient tumors.
- Novel models are needed to study resistance mechanisms.
Purpose of the Study:
- To develop and characterize 3D cancer organoids from genetically engineered mouse models (GEMMs) for BRCA1- and BRCA2-deficient cancers.
- To establish a platform for studying tumor biology and drug resistance to PARPi.
Main Methods:
- Generation of three-dimensional (3D) cancer organoids from GEMMs with BRCA1/2 deficiency.
- In vitro expansion and genetic modification of organoid cultures.
- Orthotopic transplantation of organoids into mice to form tumors.
Main Results:
- Organoid cultures were efficiently derived and expanded in vitro.
- Transplanted organoids formed tumors that mirrored the original tumor's morphology and drug response.
- GEMM-derived organoids proved amenable to genetic manipulation.
Conclusions:
- 3D organoids from GEMMs provide a robust model for studying BRCA1/2-deficient cancers.
- This model system facilitates genetic studies of tumor biology and the development of strategies to overcome PARPi resistance.
