Auranofin to prevent progression of pancreatic ductal adenocarcinoma.

236 Background: Auranofin, an FDA anti-rheumatic agent shown to have anticancer properties for lung and ovarian cancer has never been studied for pancreatic cancer. We hypothesize that Auranofin may prevent pancreatic ductal adenocarcinoma (PDAC) progression by induction of apoptosis. Methods: We performed in vitro and in vivo studies using human PDAC cell lines and patient-derived xenografts (PDX) to assess Auranofin anticancer activity. Sensitivity to the compound was determined based on IC50s. Western blot assay was used to interrogate mechanisms of apoptosis, autophagy, and resistance. Two PDAC orthotopic mouse models were designed to determine optimal dose (survival), and antitumor effect (non-survival). Results: We found more than half of PDAC cell lines (10/18) to be sensitive to Auranofin based on IC50s below 5µM. Ex vivo tissue growth inhibition greater than 44% was observed for 13 PDX tissue cases treated with 10 µM Auranofin. Treatment with low-dose Auranofin (0.5-1µM) was found to induce PARP ...