Doctor of Philosophy, The Ohio State University, 2021, Biomedical Engineering

Lung cancer is leading cause of cancer-related deaths in the United States with 5-year survival rate of 18.6%. This is due to late detection of lung cancer and problems in screening for lung cancer. Indeterminate pulmonary nodules (IPNs) are pulmonary nodules size between 7-20mm diameter solid nodules. 90% of IPNs are incidentally found and they are hard to diagnosis due to their small size and current diagnosis methods such as CT, PET scans and biopsy involve high exposure to radiation or invasive and could lead to complications. The majority of lung cancer patients have non-small cell lung cancer (NSCLC) and 64% of these patients exhibit driver mutations such as epithelial growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) and Ras mutations. These patients have shown to have improved survival rate if they are treated with targeted therapies directed against the driver mutations. Although these patients initially show strong response to targeted therapies, most patients develop resistance to these targeted treatments through secondary point mutation and epithelial to mesenchymal transition (EMT). The lung is a dynamic organ where alveolar epithelial cells are normally exposed to significant mechanical forces (i.e. ~8% cyclic strain, transmural pressure and shear stress) while primary lung tumor cells experience a 40-fold decrease in these mechanical forces/strain. Although biomechanical factors in the tumor microenvironment have been shown to be a significant driver of cancer progression, there is limited information about how biophysical forces alters drug sensitivity in lung adenocarcinoma cells. Based on the known importance of mechanical forces/strain on lung injury and repair and the significant difference in cyclic strain applied to normal and cancer cells in the lung, we hypothesized that cyclic mechanical strain would activate important oncogenic pathways and alter drug sensitivity. Although local mechanical properties of the lung tumor may (open full item for complete abstract)

Committee: Ghadiali Samir Dr. (Advisor); Joshua Englert Dr. (Committee Member); Arunark Kolipaka Dr. (Committee Member) Subjects: Biomedical Engineering