Date of Award
Master of Science (MS)
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.
Faisthalab, Raeesa, "Elucidating Mechanisms of Gefitinib Resistance that Instigate Cancer Progression." Thesis, Georgia State University, 2018.