Department of Medicine, The Mount Vernon Hospital, Mount Vernon, NY 10550, USA.
J Hematol Oncol. 2010 Feb 4;3:5. doi: 10.1186/1756-8722-3-5.
Histone deacetylases (HDACs) can regulate expression of tumor suppressor genes and activities of transcriptional factors involved in both cancer initiation and progression through alteration of either DNA or the structural components of chromatin. Recently, the role of gene repression through modulation such as acetylation in cancer patients has been clinically validated with several inhibitors of HDACs. One of the HDAC inhibitors, vorinostat, has been approved by FDA for treating cutaneous T-cell lymphoma (CTCL) for patients with progressive, persistent, or recurrent disease on or following two systemic therapies. Other inhibitors, for example, FK228, PXD101, PCI-24781, ITF2357, MGCD0103, MS-275, valproic acid and LBH589 have also demonstrated therapeutic potential as monotherapy or combination with other anti-tumor drugs in CTCL and other malignancies. At least 80 clinical trials are underway, testing more than eleven different HDAC inhibitory agents including both hematological and solid malignancies. This review focuses on recent development in clinical trials testing HDAC inhibitors as anti-tumor agents.
组蛋白去乙酰化酶 (HDACs) 可以通过改变 DNA 或染色质的结构成分来调节肿瘤抑制基因的表达和参与癌症发生和进展的转录因子的活性。最近，通过对乙酰化等方式进行基因抑制的作用在癌症患者中已经得到了临床验证，有几种 HDAC 抑制剂被 FDA 批准用于治疗皮肤 T 细胞淋巴瘤 (CTCL)，用于治疗两种全身治疗后或治疗中进展、持续或复发的疾病的患者。其他抑制剂，例如 FK228、PXD101、PCI-24781、ITF2357、MGCD0103、MS-275、丙戊酸和 LBH589，也已被证明具有治疗潜力，可作为单一药物或与 CTCL 和其他恶性肿瘤中的其他抗肿瘤药物联合使用。目前正在进行至少 80 项临床试验，测试超过 11 种不同的 HDAC 抑制药物，包括血液系统恶性肿瘤和实体瘤。本文综述了临床试验中测试 HDAC 抑制剂作为抗肿瘤药物的最新进展。
