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Characterisation of a patient-relevant tumour stromal cell signature.

Every year, breast cancer kills more Irish women than any other type of cancer. Other cells that surround cancer cells, called ‘stromal cells’ (SC) are receiving increased attention for their role in causing and maintaining breast cancer growth as well as protecting the tumour from immune cell attack. Therefore discovering a regimen to safely target SC is a key goal in breast cancer medicine. We have developed a process that allows us to specifically isolate and grow SCs from breast cancer tissue (tumour SCs-TSCs) and tumour-associated normal (TAN) tissue from the same patient. Using RNA-seq we have identified genes that are upregulated in TSCs compared to TANs. In this project, we will determine if this stromal cell signature is prevalent in a larger cohert of patients. We will also determine if manipulation (by siRNA knockdown) of these genes effects the immunomodulatory properties of TSCs. These studies will help us determine if these genes represent viable cancer therapies that target TSCs specifically, therefore reducing side-effects, such as anemia and muscle wastage. Findings from this study will be of great significance to breast cancer patients and will allow us to apply for further funding to develop and test these genes in clinically relevant breast cancer models similar to human disease. We believe new SC-based therapies such as these genes will inhibit growth and spread of breast cancer more effectively, by allowing immune cells to attack the cancer.