Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Centre for Cancer Research, University of Melbourne, Melbourne, VIC, Australia; and Department of Haematology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.
Science. 2017 Mar 17;355(6330):1147-1152. doi: 10.1126/science.aam7304. Epub 2017 Mar 16.
Cancer biology is profoundly influenced by changes in the epigenome. Because the dynamic plasticity of the epigenome lends itself well to therapeutic manipulation, the past few years have witnessed an unprecedented investment in the development, characterization, and translation of targeted epigenetic therapies. In this review, I provide a broad context for recent developments that offer a greater understanding of how epigenetic regulators facilitate the initiation, maintenance, and evolution of cancer. I discuss newly developed epigenetic therapies and the cellular and molecular mechanisms that may govern sensitivity and resistance to these agents. I also review the rationale for future combination therapies involving existing and emerging epigenetic drugs.
癌症生物学受到表观基因组变化的深刻影响。由于表观基因组的动态可塑性非常适合治疗干预,过去几年,人们对靶向表观遗传学治疗的开发、表征和转化进行了前所未有的投资。在这篇综述中,我提供了一个广泛的背景,介绍了最近的发展,这些发展使我们更好地理解了表观遗传调节剂如何促进癌症的发生、维持和进化。我讨论了新开发的表观遗传学疗法,以及可能控制对这些药物的敏感性和耐药性的细胞和分子机制。我还回顾了涉及现有和新兴表观遗传学药物的未来联合治疗的基本原理。