TY - JOUR
T1 - Epigenome Remodeling in Cholangiocarcinoma
AU - O'Rourke, Colm J
AU - Lafuente-Barquero, Juan
AU - Andersen, Jesper B
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2019/6
Y1 - 2019/6
N2 - Cholangiocarcinoma (CCA) comprises a heterogeneous collection of malignancies arising within the biliary tract, characterized by late diagnosis, innate chemoresistance, and abysmal prognosis. Sequencing data have uncovered recurrent mutations in diverse epigenetic regulators, implicating epigenetic destabilization at the root of these tumors. However, few studies have characterized biliary tumor epigenomes. In this Opinion article, we argue that an epigenome-oriented approach to CCA could establish diverse interconnections between many key aspects of research on this disease, including molecular heterogeneity, diverse cells of origin, and prominent tumor microenvironments. Moreover, we discuss plausible causes of epigenome dysregulation in biliary tumors, including genetic, epigenetic, metabolic, microenvironmental, and physiological factors. Lastly, we assess the translational potential of epigenomics in CCA to uncover robust biomarkers and therapeutic opportunities for this growing group of patients with limited treatment options.
AB - Cholangiocarcinoma (CCA) comprises a heterogeneous collection of malignancies arising within the biliary tract, characterized by late diagnosis, innate chemoresistance, and abysmal prognosis. Sequencing data have uncovered recurrent mutations in diverse epigenetic regulators, implicating epigenetic destabilization at the root of these tumors. However, few studies have characterized biliary tumor epigenomes. In this Opinion article, we argue that an epigenome-oriented approach to CCA could establish diverse interconnections between many key aspects of research on this disease, including molecular heterogeneity, diverse cells of origin, and prominent tumor microenvironments. Moreover, we discuss plausible causes of epigenome dysregulation in biliary tumors, including genetic, epigenetic, metabolic, microenvironmental, and physiological factors. Lastly, we assess the translational potential of epigenomics in CCA to uncover robust biomarkers and therapeutic opportunities for this growing group of patients with limited treatment options.
U2 - 10.1016/j.trecan.2019.05.002
DO - 10.1016/j.trecan.2019.05.002
M3 - Review
C2 - 31208696
SN - 2405-8033
VL - 5
SP - 335
EP - 350
JO - Trends in Cancer
JF - Trends in Cancer
IS - 6
ER -