Investigating the role of endometriosis-associated inflammatory signalling in ovarian clear cell carcinoma development

Ovarian cancer is the most lethal cancer of the female reproductive system and the fifth leading cause of cancer-related death in Canadian women. Ovarian cancer is not one disease, but rather comprises several tumour types that likely develop through unique mechanisms from different cell types. Previous research suggests two types of ovarian cancer — clear cell carcinoma (CCC) and endometrioid carcinoma (EC) — may develop from ovarian endometriosis, a condition associated with increased inflammation. Dr. Alicia Tone is investigating how endometriosis-associated inflammation can influence the development of CCC and EC by looking at the specific role that the ARID1A gene plays in inflammation. ARID1A has been shown to increase the activity of the glucocorticoid receptor, which plays a crucial role in reducing the duration and intensity of an inflammatory response. In addition, the ARID1A gene was recently found to be mutated in both CCC/EC, and the mutated gene is associated with endometriosis lesions. Dr. Tone intends to 1) identify which specific inflammatory genes are altered in CCC/EC cells and associated endometriosis; 2) compare the response of cells obtained from endometriosis and CCC specimens with and without mutations in the ARID1A gene; and 3) determine the mechanism by which ARID1A regulates the response to inflammatory mediators. This study will help our understanding of how endometriosis may develop into ovarian cancer (CCC and EC); more importantly, pointing to the development of new preventive strategies. Research aimed at understanding what is involved in the early stages of development of these different cancers may reduce the number of deaths associated with ovarian cancer.