Drivers of Gene Expression Dysregulation in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating disease with a poor prognosis. The functional consequences of common genetic aberrations and their roles in treatment strategies have been extensively reviewed. In addition to these genomic aberrations, consideration of non-genetic drivers of altered oncogene expression is essential to account for the diversity in PDAC phenotypes. In this review we seek to assess our current understanding of mechanisms of gene expression dysregulation. We focus on four drivers of gene expression dysregulation, including mutations, transcription factors, epigenetic regulators, and RNA stability/isoform regulation, in the context of PDAC pathogenesis. Recent studies provide much-needed insight into the role of gene expression dysregulation in dissecting tumor heterogeneity and stratifying patients for the development of personalized treatment strategies.