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Please use this identifier to cite or link to this item: http://hdl.handle.net/10713/8032

Title: DNA Methyltransferase inhibitors in Combination with PARP inhibitors Generate Synthetic Lethality in BRCA-proficient Ovarian Cancer
Stojanovic_umaryland_0373N_10959.pdf  (3.73 MB)
Authors: Stojanovic, Lora
Advisors: Rassool, Feyruz V.
Date: 2018
Abstract: Approximately 10% of Epithelial ovarian cancer (EOC) patients have BRCA mutations and are treated with FDA approved poly (ADP-ribose) polymerase (PARP) inhibitors. While some patients with BRCA wild-type EOC have shown a response, the majority of BRCA mutated EOC respond to PARPi therapy. The standard therapy for EOC patients is platinum-based chemotherapy which often leads to resistance to this treatment. Therefore, new therapies are essential for the improvement of EOC treatment. In this study we will investigate the role of low-dose epigenetic therapy in reprograming the DSB repair response to potentially induce a "BRCAness" effect that sensitizes EOC cells to PARPi. We show that 5-AZA reprograms epigenome by changing the gene expression in DNA repair genes which lead to BRCAness and results in impaired HR-mediated repair. Lastly, we will determine whether the downregulation of FANCD2, is responsible for sensitization of EOC cell to PARPi therapy that results in increased cytotoxicity.
Subject Keywords: DNA methyltransferase inhibitors
low-dose epigenetic therapy
PARP inhibitors
Ovaries--cancer--genetic aspects
Epigenesis, Genetic--physiology
Description: University of Maryland, Baltimore. Molecular Medicine. M.S. 2018
Type: dissertation
Appears in Collections:Theses and Dissertations All Schools
Theses and Dissertations School of Medicine

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