Chemotherapy and radiation induce cancer cell death through DNA damage; however, the prevalence of drug-resistant cancer presents a substantial treatment barrier. Previous investigations have connected the overexpression of DNA dependent protein kinase (DNA-PK), a crucial enzyme in the DNA damage response (DDR), to chemotherapy resistant cancer cells. There has been much evidence to indicate that chemical inhibitors of DNA-PK are able to effectively inhibit the DDR and promote cancer cell death when treated with chemotherapy. However, chemical inhibitors are only one avenue capable of achieving this outcome. Adenovirus inactivates the DDR to promote an active infection. Our lab has preliminary data indicating that the E4-11kDa viral protein inhibits DNA-PK phosphorylation, preventing it from repairing damaged DNA. Thus, the viral gene encoding the E4-11kDa protein is a strong candidate as a possible DNA-PK inhibitor to increase cancer cell death during chemotherapy and radiation treatment. Current efforts focus on using an E4-11kDa expression vector to investigate impact on DNA-PK expression and cancer cell viability with the intention of producing clinically relevant results to decrease the impact of cancer on patients.
Authors: Katelyn Wang, Christopher L. Chen, Eileen Bridge, PhD
Advisor: Eileen Bridge, Department of Microbiology
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