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

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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