Children's Brain Tumor Research Centre, University of Nottingham, UK.
Int J Cancer. 2011 Dec 15;129(12):2765-74. doi: 10.1002/ijc.26241. Epub 2011 Aug 8.
Aberrant epigenetic regulation of gene expression contributes to tumor initiation and progression. Studies from a plethora of hematologic and solid tumors support the use of histone deacetylase inhibitors (HDACi) as potent anticancer agents. The mechanism(s) of HDACi-induced cancer growth inhibition and cell death are complex and incompletely elucidated. Here, we discuss erroneous epigenetic regulation of hTERT transcription in cancer cells and propose that alleviation of an improper acetylation-deacetylation balance at the hTERT promoter, is one mode by which HDACi induces anticancer effects. We conclude with some pertinent questions and future perspectives arising from the recent impetus in HDACi preclinical and early clinical studies, with particular attention to the cancer stem cell therapeutic paradigm and its relevance to tumor resistance.
异常的基因表达表观遗传调控导致肿瘤的发生和发展。来自大量血液系统和实体肿瘤的研究支持组蛋白去乙酰化酶抑制剂（HDACi）作为有效的抗癌药物。HDACi 诱导的肿瘤生长抑制和细胞死亡的机制复杂且不完全阐明。在这里，我们讨论了癌症细胞中端粒酶逆转录酶（hTERT）转录的错误表观遗传调控，并提出 hTERT 启动子上不适当的乙酰化-去乙酰化平衡的缓解是 HDACi 诱导抗癌作用的一种模式。我们在最后提出了一些相关的问题和未来展望，这些展望来自于 HDACi 的临床前和早期临床研究的最新进展，特别关注癌症干细胞治疗范例及其与肿瘤耐药性的相关性。
