Serebrenik, Artur2021-10-132021-10-132019-08https://hdl.handle.net/11299/224953University of Minnesota Ph.D. dissertation. August 2019. Major: Pharmacology. Advisors: Reuben Harris, Hiroshi Hiasa. 1 computer file (PDF); viii, 126 pages.Cancer imposes a burden on the entire world. As of 2019, cancer accounts for 1 in every 6 deaths worldwide. This is a difficult disease to treat because of the immense heterogeneity created by mutations in tumors. These mutations allow tumors to evolve mechanism to avoid cell death, evade immune detection, develop drug resistance and metastasize. Considerable research has undergone to better understand the underlying molecular basis for the mutations observed in tumors. A better understanding of these processes is critical for development of effective therapies that kill cancer cells with minimal adverse effects. The advent of deep sequencing technologies has given researchers vast insights into the many cellular perturbations that give rise to the mutations observed in cancer. One of these molecular mechanisms is the cytosine deaminase activity attributed to the APOBEC3B (A3B) enzyme. Previous studies have implicated A3B as an endogenous source of mutation because it is overexpressed in cancerous tissue compared to normal tissue, it is active and generates detectable mutations in genomic DNA, and has clear associations with clinical outcomes. Here, we embarked on multiple approaches to identify therapeutically-relevant strategies of selectively killing A3B-expressing cancer cells. Overall, we are confident that a deeper understanding of the molecular mechanisms involved in processing A3B-catalyzed lesions will yield novel clinical opportunities.enAPOBEC mutagenesisAPOBEC3Bclear cell ovarian carcinomaplatinum chemotherapySynthetic lethalityuracil base excision repairThesis or Dissertation