Division of Hematology and Oncology, Columbia University Medical Center, William Black Building, 650 W 168th Street, Room 901, New York, NY, 10032, USA.
Curr Treat Options Oncol. 2020 Jun 29;21(8):61. doi: 10.1007/s11864-020-00761-9.
Epigenetic mutations are frequent and pathogenic in select subtypes of lymphoma, and agents modulating DNA and histone methylation-such as inhibitors of DNMT and EZH2, respectively-have demonstrated promise in treating these diseases. In particular, lymphomas derived from the germinal center-GC-DLBCL, FL, and AITL-are all characterized by epigenetic derangements. In an effort to target these derangements, DNMT inhibitors have been investigated as a means of improving responsiveness to chemotherapy in DLBCL patients, or as monotherapy or in combination with other epigenetic agents in the treatment of TCL. Histone methyltransferase inhibitors have demonstrated effectiveness in R/R FL patients with EZH2-activating mutations. New treatment options that target the pathogenesis of disease are needed. HDAC inhibitors have been in the clinic for over a decade for the treatment of lymphoma, and now methyltransferase inhibitors are finding their niche for this disease.
表观遗传突变在某些特定类型的淋巴瘤中较为常见且具有致病性，而调节 DNA 和组蛋白甲基化的药物——例如分别针对 DNMT 和 EZH2 的抑制剂——在治疗这些疾病方面显示出了一定的前景。特别是起源于生发中心的淋巴瘤——GC-DLBCL、FL 和 AITL——均具有表观遗传失调的特征。为了针对这些失调，DNMT 抑制剂已被作为提高 DLBCL 患者对化疗反应性的一种手段进行研究，或者作为单药或与其他表观遗传药物联合用于治疗 TCL。组蛋白甲基转移酶抑制剂在 EZH2 激活突变的复发/难治性 FL 患者中已显示出有效性。需要有新的针对疾病发病机制的治疗选择。HDAC 抑制剂已经在临床上应用了十余年用于治疗淋巴瘤，而现在甲基转移酶抑制剂也正在为这种疾病找到自己的定位。
