The role of polycomb repressive complexes in biliary tract cancer

Abstract

Introduction: 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.

Areas covered: 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.

Expert opinion: 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.

Keywords:

• biliary tract cancer
• BMI1
• epigenetics
• EZH2
• histone modifications
• polycomb repressive complex

Declaration of interest

C Mayr and T Kiesslich were supported by the Research fund of the Paracelsus Medical University A-12/02/006-KIE and Oesterreichische National bank, Anniversary fund 14842. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Notes

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