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

研究乳腺癌基因雌激素受体突变的重要性

基本信息

批准号：
2022896
负责人：
金额：
--
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2017
资助国家：
英国
起止时间：
2017 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-2022896
关键词：
Investigating Importance Mutations Estrogen Receptor

项目摘要

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

乳腺癌是世界范围内女性最常见的癌症，每年诊断出超过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（ER a）起作用。我们已经使用CRISPR-Cas9基因组编辑系统在充分研究和广泛使用的雌激素响应性MCF 7乳腺癌细胞系中进行基因敲入，以模拟最近在治疗抗性转移性乳腺癌（EndoR-MBC）中鉴定的主要ER α突变。这些工程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如何起作用，评估它们在转移中的作用，重要的是，确定是否可以推导出治疗EndoR-MBC疾病的合理治疗途径。该项目的一个主要优势是，它涉及一个建立良好的，领先的英国学术乳腺癌研究小组调查乳腺癌的内分泌耐药性和研发肿瘤iMed集团在阿斯利康，一家领先的全球制药公司，负责开发主要的内分泌疗法，包括芳香酶抑制剂和抗雌激素，乳腺癌之间的新合作。参考：Harrod等人，Oncogene，2017 http://www.nature.com/onc/journal/vaop/ncurrent/full/onc2016382a.html