表观遗传学在淋巴瘤治疗中的现状与前景
The Status and Prospects of Epigenetics in the Treatment of Lymphoma.
作者信息
Liu Jiaxin, Li Jia-Nan, Wu Hongyu, Liu Panpan
机构信息
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China.
出版信息
Front Oncol. 2022 Apr 8;12:874645. doi: 10.3389/fonc.2022.874645. eCollection 2022.
The regulation of gene transcription by epigenetic modifications is closely related to many important life processes and is a hot research topic in the post-genomic era. Since the emergence of international epigenetic research in the 1990s, scientists have identified a variety of chromatin-modifying enzymes and recognition factors, and have systematically investigated their three-dimensional structures, substrate specificity, and mechanisms of enzyme activity regulation. Studies of the human tumor genome have revealed the close association of epigenetic factors with various malignancies, and we have focused more on mutations in epigenetically related regulatory enzymes and regulatory recognition factors in lymphomas. A number of studies have shown that epigenetic alterations are indeed widespread in the development and progression of lymphoma and understanding these mechanisms can help guide clinical efforts. In contrast to chemotherapy which induces cytotoxicity, epigenetic therapy has the potential to affect multiple cellular processes simultaneously, by reprogramming cells to achieve a therapeutic effect in lymphoma. Epigenetic monotherapy has shown promising results in previous clinical trials, and several epigenetic agents have been approved for use in the treatment of lymphoma. In addition, epigenetic therapies in combination with chemotherapy and/or immunotherapy have been used in various clinical trials. In this review, we present several important epigenetic modalities of regulation associated with lymphoma, summarize the corresponding epigenetic drugs in lymphoma, and look at the future of epigenetic therapies in lymphoma.
表观遗传修饰对基因转录的调控与许多重要生命过程密切相关,是后基因组时代的研究热点。自20世纪90年代国际表观遗传学研究兴起以来,科学家们已鉴定出多种染色质修饰酶和识别因子,并对其三维结构、底物特异性及酶活性调控机制进行了系统研究。对人类肿瘤基因组的研究揭示了表观遗传因素与各种恶性肿瘤的密切关联,我们也更加关注淋巴瘤中表观遗传相关调控酶和调控识别因子的突变。多项研究表明,表观遗传改变在淋巴瘤的发生发展过程中确实广泛存在,了解这些机制有助于指导临床工作。与诱导细胞毒性的化疗不同,表观遗传疗法有可能通过对细胞进行重编程,同时影响多个细胞过程,从而在淋巴瘤中实现治疗效果。表观遗传单药疗法在以往临床试验中已显示出有前景的结果,多种表观遗传药物已获批用于治疗淋巴瘤。此外,表观遗传疗法与化疗和/或免疫疗法联合应用也已用于各种临床试验。在本综述中,我们介绍了与淋巴瘤相关的几种重要表观遗传调控方式,总结了淋巴瘤中的相应表观遗传药物,并展望了淋巴瘤表观遗传疗法的未来。