title: The role of polycomb repressive complexes in biliary tract cancer.
abstract: BACKGROUND
  Polycomb group proteins are major epigenetic regulators that modify histone tails. They are organized in two multi-protein complexes called polycomb repressive complex (PRC) 1 and 2. Aberrant PRC activity is known to contribute to the development and aggressiveness of many cancers. Biliary tract cancer (BTC) is a rare malignancy associated with high chemoresistance and poor clinical outcome. Here we review the role of the PRC complexes and the effects of RNAi and drug-mediated inhibition of PRC1 and PRC2 in BTC.
  
  
  METHODS
  This review gives a short overview of the composition, biochemical functions and oncogenic role of PRC complexes. We then focus on and summarize the results of current studies that address the role of PRC in BTC. Finally, we discuss options and results of therapeutic targeting of PRC in BTC.
  
  
  CONCLUSIONS
  Pharmacological inhibition of the two PRC complexes seems to be a promising strategy for treatment of BTC. To date, only few studies have addressed the therapeutic effect of PRC inhibition in BTC. Therefore, it will be important to test established PRC inhibitors, such as DZNep, as well as newly developed drugs, for example, PTC209, to gain more insight into the role of the PRC complexes in BTC and potentially to develop new therapeutic strategies.
authors.affiliation: Department of Internal Medicine I, Paracelsus Medical University / Salzburger Landeskliniken and Laboratory for Tumor Biology and Experimental Therapies, Institute of Physiology and Pathophysiology, Paracelsus Medical University , Salzburg , Austria +43 662 4482 2795 ; ch.mayr@salk.at.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayr
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Andrej
authors.initials: A
authors.lastname: Wagner
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001661:Biliary Tract Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D006657:Histones / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D063150:Polycomb Repressive Complex 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D063151:Polycomb Repressive Complex 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D034622:RNA Interference
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D063151:Polycomb Repressive Complex 2; D063150:Polycomb Repressive Complex 1
keywords: BMI1; EZH2; biliary tract cancer; epigenetics; histone modifications; polycomb repressive complex