a Xiangya Hospital, Central South University , Changsha , Hunan , China.
Expert Rev Anticancer Ther. 2019 Feb;19(2):139-149. doi: 10.1080/14737140.2019.1552139. Epub 2018 Dec 4.
: Epigenetic modification without DNA sequence mutation plays an important role in cancer development. Some small molecular inhibitors targeting key epigenetic molecules have been approved by the Food and Drug Administration to treat hematological malignancies. However, the anticancer effects of these drugs on solid tumors are not satisfactory, and the mechanisms of action remain largely unknown. : The review summarizes the latest research on cancer epigenetics and discusses the potentials and limitations of using epigenetic drugs to treat solid tumors. An analysis of possible reasons for epigenetic drug treatment failure in solid tumors in some clinical trials is discussed along with prospects for future development. : Next-generation small molecule inhibitors will target novel epigenetic regulators with high cancer specificity. Combined modalities exploiting epigenetic drugs with chemo-/radiotherapy, molecular-targeting drugs, and immunotherapy will be able to effectively treat solid tumors in the near future.
表观遗传修饰而不伴随 DNA 序列突变，在癌症的发生发展中起着重要作用。一些针对关键表观遗传分子的小分子抑制剂已被食品和药物管理局批准用于治疗血液系统恶性肿瘤。然而，这些药物对实体瘤的抗癌作用并不令人满意，其作用机制在很大程度上仍不清楚。本文综述了癌症表观遗传学的最新研究进展，并讨论了利用表观遗传药物治疗实体瘤的潜力和局限性。讨论了一些临床试验中实体瘤中表观遗传药物治疗失败的可能原因，并对未来的发展前景进行了展望。新一代的小分子抑制剂将针对具有高癌症特异性的新型表观遗传调控因子。在不久的将来，联合应用表观遗传药物与化疗/放疗、分子靶向药物和免疫疗法的联合治疗模式，将能够有效地治疗实体瘤。
