Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a marked propensity for liver metastasis and a poor overall prognosis. Although canonical driver mutations are common, metastatic dissemination cannot be fully explained by the accumulation of additional coding alterations, implicating epigenetic dysregulation as a key driver of disease progression. This dissertation examines how disruption of noncoding, chromatin-based regulatory mechanisms shapes pancreatic cancer progression, with a focus on transcriptional plasticity, immune evasion, and metastatic competence. Together, these studies provide new insight into the epigenetic basis of pancreatic cancer progression and highlight the therapeutic potential of targeting epigenetic vulnerabilities.
