Epigenetic Landscape in Pancreatic Ductal Adenocarcinoma: On the Way to Overcoming Drug Resistance?
Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia
Molecular Epidemiology and Predictive Tumor Markers Group, Medical Oncology Research Laboratory, Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9100, 28034 Madrid, Spain
Biomarkers and Therapeutic Targets Group, Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9100, 28034 Madrid, Spain
Department of Molecular Oncology, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(11), 4091; https://doi.org/10.3390/ijms21114091
Received: 2 June 2020 / Revised: 2 June 2020 / Accepted: 6 June 2020 / Published: 8 June 2020
(This article belongs to the Special Issue Attacking Cancer Progression and Metastasis)
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid malignancies due to the rapid rate of metastasis and high resistance to currently applied cancer therapies. The complex mechanism underlying the development and progression of PDAC includes interactions between genomic, epigenomic, and signaling pathway alterations. In this review, we summarize the current research findings on the deregulation of epigenetic mechanisms in PDAC and the influence of the epigenome on the dynamics of the gene expression changes underlying epithelial–mesenchymal transition (EMT), which is responsible for the invasive phenotype of cancer cells and, therefore, their metastatic potential. More importantly, we provide an overview of the studies that uncover potentially actionable pathways. These studies provide a scientific basis to test epigenetic drug efficacy in synergy with other anticancer therapies in future clinical trials, in order to reverse acquired therapy resistance. Thus, epigenomics has the potential to generate relevant new knowledge of both a biological and clinical impact. Moreover, the potential, hurdles, and challenges of predictive biomarker discoveries will be discussed, with a special focus on the promise of liquid biopsies.