a Department of Hematology , Ankara University School of Medicine, Cebeci Hospital , Mamak , Turkey.
Expert Opin Drug Saf. 2019 Jul;18(7):563-571. doi: 10.1080/14740338.2019.1615051. Epub 2019 May 9.
Dysregulation of histone deacetylase (HDAC) activity is an epigenetic hallmark of multiple myeloma (MM), leading to aberrant gene expression and cellular signaling in myeloma cell growth, survival and resistance to therapy. Hyper-methylation at diagnosis is a frequent observation, which eventually may convert to hypo-methylation during advanced phases.
A literature search on 'HDAC inhibitors' and 'multiple myeloma' was carried out using PubMed and Google Scholar in the preparation of this overview on clinical efficacy and safety data.
First-generation non-selective HDAC inhibitors have demonstrated minimal single-agent activity in refractory MM. Subsequently, combination therapy has proven an improvement in progression-free survival (PFS) but not response rates. The main concerns are associated with toxicities. Ongoing studies on new and more selective agents, i.e. Romidepsin or Ricolinostat, are promising in terms of better efficacy and less toxicity.
组蛋白去乙酰化酶（HDAC）活性失调是多发性骨髓瘤（MM）的表观遗传标志，导致骨髓瘤细胞生长、存活和对治疗的耐药性中异常基因表达和细胞信号传导。在诊断时的高甲基化是一种常见的观察结果，最终在晚期阶段可能会转变为低甲基化。
在准备关于临床疗效和安全性数据的概述时，使用 PubMed 和 Google Scholar 对“HDAC 抑制剂”和“多发性骨髓瘤”进行了文献检索。
第一代非选择性 HDAC 抑制剂在难治性 MM 中表现出最小的单药活性。随后，联合治疗已被证明可改善无进展生存期（PFS），但不能提高缓解率。主要关注点与毒性有关。正在进行的关于新型和更具选择性的药物（即罗米地辛或里克林司他）的研究在疗效更好和毒性更小方面很有希望。
