Pancreatic cancer is a deadly disease with surgery the only chance for cure. Surgeons have to evaluate whether patients with  advanced pancreatic cancer will benefit from surgery. Current diagnostic tools (imaging and CA19-9), are inadequate, with early recurrence and metastases seen in up to 40% of patients. To address this, a multi-omics approach is proposed to identify PDAC biomarkers in liquid biopsies with higher accuracy, sensitivity, and specificity. This approach involves proteomics of circulating tumor cells (CTCs) and (epi)genomics in cfDNA. We will establish a novel workflow for enrichment of CTCs from blood followed by single cell mass spectrometry. Longitudinal analysis of (epi)genetic changes in cfDNA will provide insights into what percentage of patients have detectable (epi)genetic aberrations at different stages of their disease and if this impacts prognosis. Combining information at the genome and proteome level can in the long term improve diagnostic specificity.