Abstract
Ovarian cancer is often referred to as the “silent killer” and represents the number one cause of mortality from gynaecological malignancy in women in the United Kingdom. Endometrioid ovarian cancer (EnOC) is an uncommon subtype of epithelial ovarian cancer. HOX genes have an important role in embryogenesis and development, but their role in oncogenesis is an exciting and rapidly developing field. They have been studied in many types of solid organ and haematological malignancies, including some subtypes of ovarian cancer, but not in endometrioid ovarian cancer.
This thesis shows that HOX genes are dysregulated in endometrioid ovarian cancer both at the cell line level and in a large cohort of patient tumours. Some HOX genes show heightened expression in cancerous tissue, such as HOX B5, and some HOX genes are downregulated such as HOX D10. This is proven at both an RNA level with PCR and also attempted at a protein level with IHC. However, there was no correlation between HOX gene expression and pathological or clinical variables such as stage, grade, time to progression or overall survival.
This HOX gene dysregulation can be therapeutically targeted with drugs that block HOX gene function such as the peptide HXR9. In this Thesis it is shown that HXR9 is cytotoxic to EnOC cells with an IC50 of approximately 40μM and also works in synergy with platinum chemotherapy, enhancing the sensitivity of platinum resistant ovarian cancer cells and preventing colony formation.