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

Alexandra Vivas Duarte; Ewa Gogola; Norman Sachs; Marco Barazas; Stefano Annunziato; Julian R de Ruiter; Arno Velds; Sohvi Blatter; Julia M Houthuijzen; Marieke van der Ven; Hans Clevers; Piet Borst; Jos Jonkers; Sven Rottenberg

doi:10.1038/nmeth.4535

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

Alexandra Vivas Duarte, Ewa Gogola, Norman Sachs, Marco Barazas, Stefano Annunziato, Julian R de Ruiter, Arno Velds, Sohvi Blatter, Julia M Houthuijzen, Marieke van der Ven, Hans Clevers, Piet Borst, Jos Jonkers, Sven Rottenberg

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

88 Citations (Scopus)

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.

Original language	English
Journal	Nature Methods
DOIs	https://doi.org/10.1038/nmeth.4535
Publication status	E-pub ahead of print - 11 Dec 2017

Keywords

Journal Article

Access to Document

10.1038/nmeth.4535

Cite this

@article{9f4b6026212a479d85638ad4a8b0ee84,

title = "BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance",

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.",

keywords = "Journal Article",

author = "Duarte, {Alexandra Vivas} and Ewa Gogola and Norman Sachs and Marco Barazas and Stefano Annunziato and {R de Ruiter}, Julian and Arno Velds and Sohvi Blatter and Houthuijzen, {Julia M} and {van der Ven}, Marieke and Hans Clevers and Piet Borst and Jos Jonkers and Sven Rottenberg",

year = "2017",

month = dec,

day = "11",

doi = "10.1038/nmeth.4535",

language = "English",

journal = "Nature Methods",

issn = "1548-7091",

publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - BRCA-deficient mouse mammary tumor organoids to study cancer-drug resistance

AU - Duarte, Alexandra Vivas

AU - Gogola, Ewa

AU - Sachs, Norman

AU - Barazas, Marco

AU - Annunziato, Stefano

AU - R de Ruiter, Julian

AU - Velds, Arno

AU - Blatter, Sohvi

AU - Houthuijzen, Julia M

AU - van der Ven, Marieke

AU - Clevers, Hans

AU - Borst, Piet

AU - Jonkers, Jos

AU - Rottenberg, Sven

PY - 2017/12/11

Y1 - 2017/12/11

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/nmeth.4535

DO - 10.1038/nmeth.4535

M3 - Article

C2 - 29256493

SN - 1548-7091

JO - Nature Methods

JF - Nature Methods

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this