Zang Lanlan, Kondengaden Shukkoor Muhammed, Che Fengyuan, Wang Lijuan, Heng Xueyuan
Central Laboratory and Key Laboratory of Neurophysiology, Linyi People's Hospital, Shandong University, Linyi, China.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China.
Front Mol Neurosci. 2018 Nov 15;11:408. doi: 10.3389/fnmol.2018.00408. eCollection 2018.
Glioma is characterized by a high recurrence rate, short survival times, high rates of mortality and treatment difficulties. Surgery, chemotherapy and radiation (RT) are the standard treatments, but outcomes rarely improve even after treatment. With the advancement of molecular pathology, recent studies have found that the development of glioma is closely related to various epigenetic phenomena, including DNA methylation, abnormal microRNA (miRNA), chromatin remodeling and histone modifications. Owing to the reversibility of epigenetic modifications, the proteins and genes that regulate these changes have become new targets in the treatment of glioma. In this review, we present a summary of the potential therapeutic targets of glioma and related effective treating drugs from the four aspects mentioned above. We further illustrate how epigenetic mechanisms dynamically regulate the pathogenesis and discuss the challenges of glioma treatment. Currently, among the epigenetic treatments, DNA methyltransferase (DNMT) inhibitors and histone deacetylase inhibitors (HDACIs) can be used for the treatment of tumors, either individually or in combination. In the treatment of glioma, only HDACIs remain a good option and they provide new directions for the treatment. Due to the complicated pathogenesis of glioma, epigenetic applications to glioma clinical treatment are still limited.
胶质瘤的特点是复发率高、生存时间短、死亡率高以及治疗困难。手术、化疗和放疗(RT)是标准治疗方法,但即使经过治疗,预后也很少改善。随着分子病理学的发展,最近的研究发现,胶质瘤的发生与各种表观遗传现象密切相关,包括DNA甲基化、异常微小RNA(miRNA)、染色质重塑和组蛋白修饰。由于表观遗传修饰的可逆性,调节这些变化的蛋白质和基因已成为胶质瘤治疗的新靶点。在这篇综述中,我们从上述四个方面总结了胶质瘤的潜在治疗靶点和相关有效治疗药物。我们进一步阐述了表观遗传机制如何动态调节发病机制,并讨论了胶质瘤治疗面临的挑战。目前,在表观遗传治疗中,DNA甲基转移酶(DNMT)抑制剂和组蛋白去乙酰化酶抑制剂(HDACIs)可单独或联合用于肿瘤治疗。在胶质瘤治疗中,只有HDACIs仍然是一个不错的选择,它们为治疗提供了新的方向。由于胶质瘤发病机制复杂,表观遗传学在胶质瘤临床治疗中的应用仍然有限。