Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, 147002, India.
Eur J Med Chem. 2019 Mar 15;166:351-368. doi: 10.1016/j.ejmech.2019.01.069. Epub 2019 Feb 1.
With each newly disclosed resistance mechanism, management of cancer with previously established targets have become a "failure" oriented approach. Molecular targets such as kinases did initially provide a ray of hope against cancer but with decades of struggle between novel therapeutic agents and more sophisticated resistance mechanisms, they seem to have saturated as anti-cancer targets. Now, with more exhaustive molecular recognition techniques and approaches, epigenetic targets have accessed the centre stage as anti-cancer targets. Accordingly, several classes of epigenetic enzymes are being studied for this role and histone methyltransferases form one such class. They include a class of epigenetic enzymes which transfer methyl group from histone proteins and maintain genetic homeostasis. In cancer, several reports have deduced upregulation of different members of this family according to the tumor environment, establishing them as one of the novel anti-cancer targets. This compilation provides an updated information on several members of histone methyltransferases family as epigenetic targets for developing novel anti-cancer agents.
随着每一种新披露的耐药机制的出现，以前确立的靶点的癌症治疗已经成为一种“失败”导向的方法。激酶等分子靶点最初确实为对抗癌症带来了一线希望，但经过几十年的新型治疗药物与更复杂的耐药机制之间的斗争，它们似乎已经作为抗癌靶点而饱和。现在，随着更详尽的分子识别技术和方法的出现，表观遗传靶点已经成为抗癌靶点的中心舞台。相应地，正在研究几类表观遗传酶来发挥这一作用，组蛋白甲基转移酶就是其中之一。它们包括一类将甲基基团从组蛋白蛋白转移并维持遗传平衡的表观遗传酶。在癌症中，根据肿瘤环境，有几项报告推断出该家族的不同成员上调，将其确立为新的抗癌靶点之一。本综述提供了关于组蛋白甲基转移酶家族的几个成员作为开发新型抗癌药物的表观遗传靶点的最新信息。
