BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance
| Autor: | Julian R. de Ruiter, Sohvi Blatter, Marieke van de Ven, Norman Sachs, Piet Borst, Stefano Annunziato, Hans Clevers, Arno Velds, Alexandra A. Duarte, Sven Rottenberg, Ewa Gogola, Jos Jonkers, Marco Barazas, Julia M. Houthuijzen |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
ATP Binding Cassette Transporter Subfamily B Antineoplastic Agents Mammary Neoplasms Animal Drug resistance Poly(ADP-ribose) Polymerase Inhibitors Biology Biochemistry Mice 03 medical and health sciences Organ Culture Techniques medicine Organoid Journal Article Animals Neoplasm Molecular Biology Cell Proliferation BRCA2 Protein Mice Knockout Mammary tumor BRCA1 Protein Tumor Suppressor Proteins Cancer Cell Biology medicine.disease In vitro 3. Good health Genetically modified organism Organoids 030104 developmental biology Drug Resistance Neoplasm Genetically Engineered Mouse Cancer research Female Biotechnology |
| Zdroj: | Nature Methods. Nature Publishing Group Nature Methods, 15(2), 134. Nature Publishing Group Nature Methods |
| ISSN: | 1548-7091 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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