Advances in Epigenetic Cancer Therapeutics

被引:28
作者
Hillyar, Christopher [1 ]
Rallis, Kathrine S. [1 ]
Varghese, Jajini [2 ,3 ]
机构
[1] Queen Mary Univ London, Barts & London Sch Med & Dent, Oncol, London, England
[2] UCL, Inst Surg & Intervent Sci, Breast & Plast Surg, London, England
[3] Royal Free NHS Trust, London, England
关键词
cancer; epigenetics; dna methylation; histone modifications; inhibitors; histone methyltransferase; histone demethylase; histone acetyltransferase; histone deacetylase; INHIBITOR; CELLS; C646;
D O I
10.7759/cureus.11725
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cancer has traditionally been hailed a genetic disease, dictated by successive genetic aberrations which alter gene expression. Yet, recent advances in molecular sequencing technologies, enabling the characterisation of cancer patient phenotypes on a large scale, have highlighted epigenetic changes as a hallmark of cancer. Epigenetic modifications, including DNA methylation and demethylation and histone modifications, have been found to play a key role in the pathogenesis of a wide variety of cancers through the regulation of chromatin state, gene expression and other nuclear events. Targeting epigenetic aberrations offers remarkable promise as a potential anti-cancer therapy given the reversible nature of epigenetic changes. Hence, epigenetic therapy has emerged as a rapidly advancing field of cancer research. A plethora of epigenetic therapies which inhibit enzymes of post-translational histone modifications, so-called 'writers', 'erasers' and 'readers', have been developed, with several epigenetic inhibitor agents approved for use in routine clinical practice. Epigenetic therapeutics inhibit the methylation or demethylation and acetylation or deacetylation of DNA and histone proteins. Their targets include writers (DNA methyltransferases [DNMT], histone acetyltransferases [HAT] and histone deacetylases [HDAC]) and erasers (histone demethylases [HDM] and histone methylases [HMT]). With new epigenetic mechanisms increasingly being elucidated, a vast array of targets and therapeutics have been brought to the fore. This review discusses recent advances in cancer epigenetics with a focus on molecular targets and mechanisms of action of epigenetic cancer therapeutics.
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页数:9
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