Ren Liwen, Yang Yihui, Li Wan, Yang Hong, Zhang Yizhi, Ge Binbin, Zhang Sen, Du Guanhua, Wang Jinhua
The State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Beijing, China.
Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Genet. 2023 Jan 4;13:1085391. doi: 10.3389/fgene.2022.1085391. eCollection 2022.
Tumor development is frequently accompanied by abnormal expression of multiple genomic genes, which can be broadly viewed as decreased expression of tumor suppressor genes and upregulated expression of oncogenes. In this process, epigenetic regulation plays an essential role in the regulation of gene expression without alteration of DNA or RNA sequence, including DNA methylation, RNA methylation, histone modifications and non-coding RNAs. Therefore, drugs developed for the above epigenetic modulation have entered clinical use or preclinical and clinical research stages, contributing to the development of antitumor drugs greatly. Despite the efficacy of epigenetic drugs in hematologic caners, their therapeutic effects in solid tumors have been less favorable. A growing body of research suggests that epigenetic drugs can be applied in combination with other therapies to increase efficacy and overcome tumor resistance. In this review, the progress of epigenetics in tumor progression and oncology drug development is systematically summarized, as well as its synergy with other oncology therapies. The future directions of epigenetic drug development are described in detail.
肿瘤发展常常伴随着多个基因组基因的异常表达,这大致可视为肿瘤抑制基因表达降低和癌基因表达上调。在此过程中,表观遗传调控在不改变DNA或RNA序列的情况下对基因表达的调节起着至关重要的作用,包括DNA甲基化、RNA甲基化、组蛋白修饰和非编码RNA。因此,针对上述表观遗传调控研发的药物已进入临床应用或临床前及临床研究阶段,极大地推动了抗肿瘤药物的发展。尽管表观遗传药物在血液系统癌症中疗效显著,但其在实体瘤中的治疗效果却不太理想。越来越多的研究表明,表观遗传药物可与其他疗法联合应用,以提高疗效并克服肿瘤耐药性。在本综述中,系统总结了表观遗传学在肿瘤进展和肿瘤学药物研发方面的进展,以及其与其他肿瘤学疗法的协同作用。还详细描述了表观遗传药物研发的未来方向。