Epigenetics in Pancreatic Ductal Adenocarcinoma: Impact on Biology and Utilization in Diagnostics and Treatment

SIMPLE SUMMARY: Epigenetic alterations contribute to the distinct biology of pancreatic ductal adenocarcinoma (PDAC) and thus allow a better understanding of molecular mechanisms active in progression, metastasis and therapeutic resistance. Exploiting such knowledge for the development and instalment of clinically impactful biomarkers and epigenetically targeted therapies will open novel and improved avenues for personalized patient care. In this review, we aim to summarize the recent advances in PDAC biology, biomarker development and therapeutic options from an epigenetic perspective. ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies with high potential of metastases and therapeutic resistance. Although genetic mutations drive PDAC initiation, they alone do not explain its aggressive nature. Epigenetic mechanisms, including aberrant DNA methylation and histone modifications, significantly contribute to inter- and intratumoral heterogeneity, disease progression and metastasis. Thus, increased understanding of the epigenetic landscape in PDAC could offer new potential biomarkers and tailored therapeutic approaches. In this review, we shed light on the role of epigenetic modifications in PDAC biology and on the potential clinical applications of epigenetic biomarkers in liquid biopsy. In addition, we provide an overview of clinical trials assessing epigenetically targeted treatments alone or in combination with other anticancer therapies to improve outcomes of patients with PDAC.