Zwergel Clemens, Romanelli Annalisa, Stazi Giulia, Besharat Zein Mersini, Catanzaro Giuseppina, Tafani Marco, Valente Sergio, Mai Antonello
Department of Drug Chemistry and Technologies, Sapienza University of Rome, Rome, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Front Pediatr. 2018 Dec 3;6:370. doi: 10.3389/fped.2018.00370. eCollection 2018.
Medulloblastoma is one of the most frequent among pediatric brain tumors, and it has been classified in various subgroups. Some of them already benefit from quite good therapeutic options, whereas others urgently need novel therapeutic approaches. Epigenetic modulators have long been studied in various types of cancer. Within this review, we summarize the main preclinical studies regarding epigenetic targets (such as HDAC, SIRT, BET, EZH2, G9a, LSD1, and DNMT) inhibitors in medulloblastoma. Furthermore, we shed light on the increasing number of applications of drug combinations as well as hybrid compounds involving epigenetic mechanisms. Nevertheless, in the studies published so far, mainly un-specific or old modulators have been used, and the PKs (brain permeability) have not been well-evaluated. Thus, these findings should be considered as a starting point for further improvement and not as a final result.
髓母细胞瘤是儿童脑肿瘤中最常见的肿瘤之一，它已被分为多个亚组。其中一些亚组已经受益于相当不错的治疗方案，而其他亚组则迫切需要新的治疗方法。长期以来，表观遗传调节剂一直在各类癌症中进行研究。在本综述中，我们总结了关于髓母细胞瘤中表观遗传靶点（如组蛋白去乙酰化酶、沉默调节蛋白、溴结构域和额外末端结构域、EZH2、G9a、赖氨酸特异性去甲基化酶1和DNA甲基转移酶）抑制剂的主要临床前研究。此外，我们还阐述了涉及表观遗传机制的药物组合以及杂合化合物的应用日益增多的情况。然而，在迄今为止发表的研究中，主要使用的是非特异性或旧的调节剂，并且药物动力学（脑通透性）尚未得到充分评估。因此，这些发现应被视为进一步改进的起点，而不是最终结果。
