Epigenetic Landscape in Pancreatic Ductal Adenocarcinoma: On the Way to Overcoming Drug Resistance?

International Journal of Molecular Sciences

MaríaLaura García Bermejo¹  Viola Stevurkova²  Sona Ciernikova²  Bozena Smolkova³  Alfredo Carrato⁴  Julie Earl⁴ 

[1] Biomarkers and Therapeutic Targets Group, Ramón y Cajal Health Research Institute (IRYCIS), Carretera Colmenar Km 9100, 28034 Madrid, Spain;Department of Genetics, Cancer Research Institute, Biomedical Research Center of the Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia;Department of Molecular Oncology, 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;

关键词: pancreatic ductal adenocarcinoma;    drug resistance;    epigenetics;    epithelial–mesenchymal transition;    liquid biopsy;    epi-drugs;   

DOI  :  10.3390/ijms21114091

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown