PROJECT SUMMARY/ABSTRACTPancreatic ductal adenocarcinoma (PDAC) has an overall survival rate of 9% and detection of PDAC is a highpriority area for the NCI. Only 10-20% of patients with PDAC have a primarily resectable disease while 50-60% of patients are diagnosed with irresectable disease. Neoadjuvant chemotherapy maybe beneficial tothese patients. Disease monitoring of PDAC patients in the neoadjuvant setting is by Computed tomography(CT) or detection of CA19-9 levels. These approaches can be imprecise and not predictive of tumor burden.Thus there is a need to develop sensitive and specific biomarkers to assess disease burden and monitorpatients with PDAC undergoing neoadjuvant therapy. Recently we showed that aberrant DNA methylationanalysis in cell-free DNA may be an attractive liquid biopsy approach for the detection of PDAC. The objectiveof this proposal is to validate our liquid biopsy approach and demonstrate its utility. In Aim 1 we will validateour Methyl 10 biomarkers for the detection of early-stage PDAC. In Aim 2 we investigate whether our Methyl10 biomarkers can detect minimal residual disease in pancreatic cancer patients. At the completion of thesestudies we will have validated and developed a novel DNA methylation biomarker set that is highly robust inthe detection of PDAC and highlight its clinical significance for monitoring treatment strategies in PDACpatients.