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Novel therapeutic targets for CCNE1-amplified high-grade serous ovarian carcinomas

Michael Herman Chui

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Canadian Institutes of Health Research (CIHR)
High-grade serous ovarian carcinoma is the leading cause of death from gynecologic cancer, with mortality rates between 70-90%. There is, therefore, a critical need to develop more effective therapeutics to treat this disease. In roughly 20% of patient tumours, there are extra copies of the cancer gene, CCNE1. This feature is associated with resistance to chemotherapy and poor survival outcome; presently, there are no targeted therapies available for this subset of ovarian cancers. In our previous work, we have screened through the genome and identified a list of potential candidate essential genes in ovarian cancers with extra copies of CCNE1. In this proposal, we will test the effects of turning off these specific genes in serous ovarian cancer cells. The most promising candidate gene will then be investigated further to delineate its role in keeping cancer cells alive. We will also measure this gene in human tumour tissues to determine whether it can predict patient outcomes. Finally, we will evaluate a targeted therapy against this essential gene in animal models and identify biomarkers for predicting which tumours would respond to treatment. The work described will enable us to develop a novel treatment for an aggressive subset of serous ovarian cancer and a diagnostic test to guide selection of patients for clinical trial enrollment.

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