Integrated PhD Biomedical Science

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Ovarian cancer causes approximately 1420,000 deaths each year. Due to the late onset of symptoms, ovarian cancer is typically diagnosed at a late stage meaning that prognosis is poor for the majority of patients. High-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer, but also the deadliest. First-line treatment for patients with HGSOC consists of cytoreductive surgery and platinum chemotherapy. Unfortunately, although HGSOC initially responds well to chemotherapy, most patients will relapse and become resistant. Platinum chemotherapy has been shown to alter the interaction between cancer cells and their environments in HGSOC. An association has also been seen between therapy resistance and upregulation of tumour microenvironment (TME) pathways, suggesting that the TME plays a key role in therapy resistance. However, the exact role of the TME in therapy resistance is yet to be fully elucidated. This project will use a decellularized mouse model of HGSOC to investigate the effect of the TME on therapy resistance to determine if cancer cell killing is reduced when cells are cultured on a chemoresistant matrix compared to a chemosensitive matrix. Additionally the ECM will be studied to determine if changes in the ECM of the chemoresistant matrix allow it to provide a chemoprotective niche to chemosensitive cells.