Elucidating mechanisms that enhance metastatic phenotypes through pharmacological ascorbate and fluid shear stress resistance

The motivation for initiating Chapter 2 was due to the clinical outcomes in the Phase I and II PDAC pharmacological ascorbate (P-AscH) trials. Patients treated with intravenous injections of P-AscH in combination with standard-of-care therapy demonstrated a significant increase in overall survival and progression free survival. Despite these encouraging results, approximately 30% of patients did not respond to this treatment regimen. To elucidate mechanisms of resistance to P-AscH, I developed two pancreatic cancer cell lines. Despite originating from the same cancer type, the two P-AscH resistant (AR) cell lines developed unique mechanisms to tolerate treatments to P-AscH.