表观遗传抗肿瘤药物的研发进展

Advances in epigenetic anti-tumor drug development

表观遗传是指在不改变DNA序列的情况下,基因功能产生可遗传的变异,并最终导致生物表型改变的生物学现象。近年来,随着表观遗传与转录等生物过程间的关系不断被揭示,研究者逐渐认识到表观调控异常也是肿瘤发生的原因之一,这为以表观遗传元件为靶点的抗肿瘤药物的研发奠定了基础。目前,在这类药物研发领域内已有多个化合物获批上市,但其临床应用和药物种类仍存在局限性。本文以表观遗传为出发点,对表观遗传抗肿瘤药物研发热点和进展进行介绍,讨论了以编码器、擦除器和阅读器等表观元件为靶点的抑制剂研究现状和临床应用情况。分析当前表观遗传抗肿瘤药物发展的困境,对未来药物临床应用策略和研发趋势进行展望。

Epigenetics refers to the processes that cellular phenotype is affected by modifications and structural changes in DNA,RNA,and histone,but without changes in DNA sequences.Recently,as functions of epigenetic in some biological processes have been revealed,people gradually recognize that epigenetic dysregulation is closely correlated with tumorigenesis and cancer progression,which provide a solid foundation for the development of anti-tuomor epigenetic drugs.Several epigenetic drugs,including small molecule inhibitors targeting epigenetic regulators like writers,erasers,and readers,have been approved in the past decade.However,problems have emerged in the development of new epigenetic anticancer drugs.For example,drug types and their clinical applications are still limited.In this review,the latest advances in epigenetic antitumor drug development have been introduced and clinical application of promising epigenetic antitumor compound shave been listed.In addition,we also analyze the dilemma and explore future evelopment and application strategies for new epigenetic antitumor drugs.