DNA Methyltransferase Inhibitors in Combination with PARP inhibitors Generate Synthetic Lethality in BRCA-proficient Ovarian Cancer
by
 
Stojanovic, Lora, author.

Title
DNA Methyltransferase Inhibitors in Combination with PARP inhibitors Generate Synthetic Lethality in BRCA-proficient Ovarian Cancer

Author
Stojanovic, Lora, author.

ISBN
9780438127531

Personal Author
Stojanovic, Lora, author.

Physical Description
1 electronic resource (58 pages)

General Note
Source: Masters Abstracts International, Volume: 57-06M(E).
 
Advisors: Feyruz V. Rassool Committee members: Rena Lapidus; Dana Roque.

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.

Local Note
School code: 0373

Subject Term
Molecular biology.

Added Corporate Author
University of Maryland, Baltimore. Molecular Medicine.

Electronic Access
http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:10815850


Shelf NumberItem BarcodeShelf LocationShelf LocationHolding Information
XX(693040.1)693040-1001Proquest E-Thesis CollectionProquest E-Thesis Collection