Author ORCID Identifier

https://orcid.org/0009-0000-3531-2897

Date Available

8-1-2024

Year of Publication

2024

Degree Name

Doctor of Philosophy (PhD)

Document Type

Doctoral Dissertation

College

Medicine

Department/School/Program

Toxicology and Cancer Biology

First Advisor

Dr. Xiaoqi Liu

Abstract

Prostate cancer (PCa) remains the most diagnosed cancer among men in the United States. There are various therapeutic routes that are implored to combat this fatal disease, and our work aims to increase the options made available to PCa patients. A combination treatment of Enzalutamide (Enz), an FDA approved drug for castration-resistant PCa patients, and Metformin, an FDA approved drug for type 2 diabetes, was utilized to enhance the efficacy of Enz in Enz-resistant PCa, both in vitro and in vivo. Thymic Lymphoma is one of the most common malignancies that can occur in various tissues and organs. Genomic stability remains a crucial cellular characteristic that prevents carcinogenesis. Within the DDR for double strand breaks (DSB), the Mre11a protein is crucial for signaling activation of ataxia-telangiectasia mutated (ATM) and performing DNA end resection during homologous recombination (HR). Our lab has demonstrated that polo-like kinase 1 (PLK1), together with casein kinase 2 (CK2), phosphorylates Mre11a during G2 DNA damage checkpoint, to prematurely terminate the DDR signaling pathway, inhibiting DNA repair during irradiation (IR) associated carcinogenesis. In this study, we aim to determine if PLK1 phosphorylation of Mre11aSSDD can prevent radiation-induced carcinogenesis in vitro and in vivo.

Digital Object Identifier (DOI)

https://doi.org/10.13023/etd.2024.259

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