Investigating The Importance Of Mutations In The Estrogen Receptor-a Gene In Breast Cancer

乳腺癌是全球女性最常见的癌症，每年确诊的病例超过150万例。每年有50万妇女死于这种疾病。乳腺癌的一个关键驱动因素是雌激素，它通过激活雌激素受体蛋白(ERA)发挥作用。我们使用CRISPR-Cas9基因组编辑系统在研究良好和广泛使用的雌激素反应性乳腺癌MCF7细胞系中制作基因敲击信号，以模拟最近在耐药转移性乳腺癌(Endor-MBC)中发现的主要ERA突变。这些工程化细胞系是一种独特而复杂的细胞资源，其目的是研究这些突变是如何发挥作用的，评估它们在转移中的作用，以及重要的是，确定是否可以推导出治疗Endor-MBC病的合理路线。这个项目的一个主要优势是，它涉及一个成熟的、领先的英国乳腺癌学术研究小组和阿斯特拉捷利康的肿瘤学IMED研发小组之间的新合作。阿斯特拉捷利康是一家全球领先的制药公司，负责开发乳腺癌的主要内分泌疗法，包括芳香酶抑制剂和抗雌激素。参考文献：Harrod et al，Oncogene，2017 http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016382a.html

Breast cancer is the most common cancer in women Worldwide, with more than 1.5 million cases diagnosed each year. Half a million women die of the disease every year. A critical driver of breast cancer is the hormone estrogen, which works by activating the estrogen receptor protein (ERa). We have used the CRISPR-Cas9 genome editing system to make gene knockins in the well studied and widely used estrogen responsive MCF7 breast cancer cell line to model the major ERa mutations recently identified in treatment-resistant, metastatic breast cancer (EndoR-MBC). These engineered lines are a unique and sophisticated cell resource, which has been made with the purpose of investigating how these mutations act, evaluating their role in metastasis and, importantly, determining if a rationalised route to the treatment can be deduced for the treatment of EndoR-MBC disease. A major strength of this project is that it involves a new collaboration between a well established, leading UK academic breast cancer research group investigating endocrine resistance in breast cancer and the R&D Oncology iMed group at Astra Zeneca, a leading global pharmaceutical company responsible for the development of major endocrine therapies, including aromatase inhibitors and anti-estrogens, for breast cancer.Reference: Harrod et al , Oncogene, 2017 http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016382a.html