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Unraveling the chemo-resistant properties of tumour-associated stromal cells within the breast tumour microenvironment.

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 tumour growth and metastasis as well as protecting the tumour from immune cell attack1. Importantly, a stroma-related gene signature predicts resistance to chemotherapy in breast cancer2. Therapies directed to cancer cells fail to eradicate SCs which contribute to chemo-resistance, reestablishing a tumourigenic milieu and favouring recurrence3. Thus understanding the mechanisms that protect SCs within the TME from the cytotoxic effects of chemotherapy may unravel new therapeutic strategies that reduce tumourigenesis, chemo-resistance and ultimately recurrence. 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-SC) tissue from the same patient. We will treat these patient-derived SC populations with various chemotherapeutic agents to determine the effect of these drugs on the survival, DNA damage response (DDR) pathways and tumour-promoting activities of these cells. These studies are significant as they will help us identify pathways that contribute to chemo-resistance in SCs within the TME. Findings from this study will be of great significance to breast cancer patients as in future experiments this information could be used to inform patient-specific SC therapeutic strategies.