组蛋白修饰是一种表观遗传机制,已知这些蛋白质的失调与癌症的发生和发展有关。在寻找新的和更有效的药物的开发,组蛋白修饰被确定为可能的治疗靶标。组蛋白甲基转移酶(HMT)抑制剂对应于能够写入或删除表观遗传信息的第三代表观遗传药物。本文系统综述了不同HMT抑制剂在癌症治疗中的应用进展和前景。在CENTRAL进行了电子搜索,临床试验,Embase,LILACS,LIVIVIVO,打开灰色,PubMed,Scopus,和WebofScience。根据标题和摘要,两名作者独立选择了符合条件的研究.在完整阅读了文章之后,根据资格标准,11项研究纳入审查。不同的HMT抑制剂已经在多个临床研究中被探索,并显示出相当大的抗肿瘤作用。然而,很少有第二阶段研究已经完成和/或有可用的结果。最先进的临床试验主要包括tazemetostat,zeste同源物2(EZH2)抑制剂的增强子被批准用于滤泡性淋巴瘤(FL)。HMT抑制剂的使用已经提出,到目前为止,血液癌症治疗的简明结果,此外,使用这些药物(单独或联合使用)后出现的不良反应对患者来说并不存在高风险.这些发现,除了正在进行的临床研究,关于HMT抑制剂在治疗不同类型的癌症中的用途,可以代表一个有希望的未来。
Histone modifications are an epigenetic mechanism, and the dysregulation of these proteins is known to be associated with the initiation and progression of cancer. In the search for the development of new and more effective drugs, histone modifications were identified as possible therapeutic targets. Histone methyltransferase (HMT) inhibitors correspond to the third generation of epigenetic drugs capable of writing or deleting epigenetic information. This systematic
review summarized the development and prospect for the use of different HMT inhibitors in cancer therapy. An electronic search was applied across CENTRAL, Clinical Trials, Embase, LILACS, LIVIVO, Open Gray, PubMed, Scopus, and Web of Science. Based on the title and abstracts, two authors independently selected eligible studies. After the complete reading of the articles, based on the eligibility criteria, 11 studies were included in the
review. Different inhibitors of HMT have been explored in multiple clinical studies, and have shown considerable anti-tumor effects. However, few phase 2 studies have been completed and/or have available results. The most advanced clinical trials mainly include tazemetostat, an Enhancer of zeste homolog 2 (EZH2) inhibitor approved for follicular lymphoma (FL). The use of HMT inhibitors has presented, so far, concise results in the treatment of hematological cancers, moreover, the adverse effects presented after the use of these medicines (alone or in combination) did not show a high level of risk for the patient. These findings, in addition to ongoing clinical studies, can represent a promising future regarding the use of HMT inhibitors in treating different types of cancer.