Date of Award

5-2-2018

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Imoh Okon

Second Advisor

Ming-Hui Zou

Third Advisor

Ping Song

Abstract

In recent years, cancer treatments have progressed substantially. However, the tumor microenvironment is dynamic and continuously evolving thereby resulting in decreased efficacy to therapies, and resistant cancer cells. The development of drug resistance in cancer patients may potentially trigger or instigate disease progression in the presence of therapeutic interventions. In this study, we investigated effects of chronic Gefitinib treatments in a lung cancer cell line model. Gefitinib is a tyrosine kinase inhibitor targeting specific mutations within the epidermal growth factor receptor (EGFR). Lung cancer cells treated for extended periods of time with Gefitinib displayed resistant phenotypes, typically characterized by DNA damage, epithelial- mesenchymal transition (EMT) as well as heightened and sustained levels of reactive oxygen species (ROS). Furthermore, we uncovered novel cancer resistant phenotypes, namely dysregulated mitochondrial biogenesis, endoplasmic reticulum (ER) alterations, cellular calcium levels and propensity towards bypassing senescence.

Available for download on Wednesday, April 22, 2020

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