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Previously, we defined a role for a molecule called CART in influencing the outcome of breast cancer and the response of patients to the most common drug used to treat the disease (tamoxifen). This project aims to characterise the way in which CART causes breast tumours to become resistant to this drug. To do this we will examine how CART interacts with the main target of tamoxifen (the estrogen receptor, or ER) and what the effects of that interaction are. We will also identify other key factors that interact with CART and ER and then examine how modulating their expression in a model system of breast cancer influences the response of the breast cancer cells to tamoxifen. For this, we will use a powerful new approach that selectively switches off all of the factors we identify and allows us to look for new targets that will re-sensitize breast cancer cells to tamoxifen. In this manner we hope to further characterise the role of CART in breast cancer progression and response to therapy, identify novel therapeutic options to complement or replace existing therapies and provide additional support for the use of CART to determine appropriate treatment for breast cancer patients.
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