期刊
EXPERT OPINION ON THERAPEUTIC TARGETS
卷 19, 期 3, 页码 363-375出版社
TAYLOR & FRANCIS LTD
DOI: 10.1517/14728222.2014.986460
关键词
biliary tract cancer; BMI1; epigenetics; EZH2; histone modifications; polycomb repressive complex
资金
- Research fund of the Paracelsus Medical University [A-12/02/006-KIE]
- Oesterreichische National bank [14842]
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.
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