BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance.

Duarte, Alexandra A; Gogola, Ewa; Sachs, Norman; Barazas, Marco; Annunziato, Stefano; R de Ruiter, Julian; Velds, Arno; Blatter, Sohvi Tuulikki; Houthuijzen, Julia M; van de Ven, Marieke; Clevers, Hans; Borst, Piet; Jonkers, Jos; Rottenberg, Sven (2018). BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance. Nature methods, 15(2), pp. 134-140. Nature Publishing Group 10.1038/nmeth.4535

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Blatter, Sohvi Tuulikki and Rottenberg, Sven

Subjects:

500 Science > 570 Life sciences; biology
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1548-7091

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Achim Braun Parham

Date Deposited:

18 Apr 2018 16:58

Last Modified:

18 Apr 2018 17:07

Publisher DOI:

10.1038/nmeth.4535

PubMed ID:

29256493

BORIS DOI:

10.7892/boris.112029

URI:

https://boris.unibe.ch/id/eprint/112029

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