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.

中文翻译：

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缺乏BRCA的小鼠乳腺肿瘤类器官来研究抗癌药物。

聚（ADP-核糖）聚合酶抑制（PARPi）是一种有前途的新治疗方法，用于治疗显示同源重组缺陷（HRD）的癌症。尽管PARPi在缺乏BRCA1或BRCA2的抑癌功能的肿瘤中成功靶向HRD，但耐药性仍是主要障碍。我们开发了源自​​BRCA1和BRCA2缺陷型癌症的基因工程小鼠模型（GEMM）的三维癌症类器官。与常规细胞系或乳球体不同，类器官培养物可以有效地衍生并在体外迅速扩增。原位移植的类器官产生了乳腺肿瘤，该乳腺肿瘤概括了上皮形态并保留了原始肿瘤的药物反应。值得注意的是，GEMM肿瘤衍生的类器官可以很容易地进行基因修饰，