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Ovarian cancer is the most deadly gynecological cancer, ranking fifth in cancer deaths among women in the United States. One subset of ovarian cancer, high-grade serous, (HGSOC) is the most dominant and malignant subtype diagnosed clinically. Current standard-of-care treatments for HGSOC, such as platinum agents and poly-ADP ribose polymerase (PARP) inhibitors, rely on defective homologous ... read morerecombination (HR) repair genes for efficacy. 15-20% of HGSOC patients have an amplification of CCNE1, which is mutually exclusive with HR-deficiency, leaving these patients with limited treatment options and poor prognoses. CCNE1 encodes the cell cycle protein Cyclin E1, which partners with cyclin-dependent kinase 2 (CDK2) to coordinate progression through the G1/S checkpoint between growth and replication. Amplification of CCNE1 is associated with hyperactive CDK2 activity. For this reason, a cyclin-dependent kinase 2 inhibitor (CDK2i) is a promising therapeutic option for this population. To observe the efficacy of CDK2i in a clinically relevant model, we attempted to engineer an isogenic model of CCNE1-amplified HGSOC in the cell-of-origin of HGSOC, fallopian tube secretory epithelial cells (FTSEC) through compromise of p53, encoded by TP53, and overexpression of CCNE1.
Thesis (B.S.)--Tufts University, 2023.
Submitted to the Dept. of Biology.read less
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