Abstract 1190 Investigating chemoresistance mechanisms and collateral responses in pancreatic ductal adenocarcinoma

Despite great effort in the development of treatment strategies for pancreatic ductal adenocarcinoma (PDAC), response rates to current gold standard chemotherapies such as 5-fluorouracil (5-FU) and gemcitabine remain low. One possible explanation for low response rates involves intrinsic or acquired chemotherapy resistance. This study aims to develop chemoresistant PDAC cell models for investigations into chemoresistance mechanisms and novel combination therapies for chemoresistant PDAC. Currently, Panc 04.03 cell lines have undergone several rounds of treatment with gradual increases in the concentration of 5-FU to evolve 5-FU resistant cell populations. Cell viability analysis of 5-FU treated PDAC cells through the CellTiterGlo assay has revealed increased sensitivity to the chemotherapy gemcitabine, a phenomenon known as collateral sensitivity. Future work will increase 5-FU resistance levels through additional treatments of 5-FU and screen common chemotherapies against 5-FU resistant PDAC cells to identify collateral responses. Taken together, this work provides a model to study chemotherapy resistance in PDAC and opens avenues for the discovery of novel treatments for chemoresistant PDAC. This research was supported by the Elon University Undergraduate Research Program, a Glen Raven Fellowship, and Elon University's Daniel Cavarretta Award (C.D.).