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

被引:24
作者
Ciernikova, Sona [1 ]
Earl, Julie [2 ]
Garcia Bermejo, Maria Laura [3 ]
Stevurkova, Viola [1 ]
Carrato, Alfredo [2 ]
Smolkova, Bozena [4 ]
机构
[1] Slovak Acad Sci, Canc Res Inst, Dept Genet, Biomed Res Ctr, Dubravska Cesta 9, Bratislava 84505, Slovakia
[2] Ramon y Cajal Hlth Res Inst IRYCIS, Med Oncol Res Lab, Mol Epidemiol & Predict Tumor Markers Grp, Carretera Colmenar Km 9100, Madrid 28034, Spain
[3] Ramon y Cajal Hlth Res Inst IRYCIS, Biomarkers & Therapeut Targets Grp, Carretera Colmenar Km 9100, Madrid 28034, Spain
[4] Slovak Acad Sci, Canc Res Inst, Dept Mol Oncol, Biomed Res Ctr, Dubravska Cesta 9, Bratislava 84505, Slovakia
关键词
pancreatic ductal adenocarcinoma; drug resistance; epigenetics; epithelial-mesenchymal transition; liquid biopsy; epi-drugs; CIRCULATING TUMOR-CELLS; MESENCHYMAL TRANSITION; E-CADHERIN; PROMOTES METASTASIS; CANCER; EXPRESSION; MICRORNA; DIAGNOSIS; BIOMARKER; DNA;
D O I
10.3390/ijms21114091
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
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.
引用
收藏
页码:11 / 17
页数:17
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