Am J Transl Res. 2011;3(5):454-67. Epub 2011 Oct 10.
Histone deacetylase inhibitors have emerged as a new class of anticancer therapeutic drugs. Their clinical utility in oncology stems from their intrinsic cytotoxic properties and combinatorial effects with other conventional cancer therapies. To date, the histone deacetylase inhibitors suberoylanilide hydroxamic acid (Vorinostat, Zolinza®) and depsipeptide (Romidepsin, Istodax®) have been approved by the US Food and Drug Administration for the treatment of refractory cutaneous T-cell lymphoma. Further, there are currently over 100 clinical trials involving the use of histone deacetylase inhibitors in a wide range of solid and hematological malignancies. The therapeutic potential of histone deacetylase inhibitors has also been investigated for numerous other diseases. For example, the cytotoxic properties of histone deacetylase inhibitors are currently being harnessed as a potential treatment for malaria, whereas the efficacy of these compounds for HIV relies on de-silencing latent virus. The anti-inflammatory properties of histone deacetylase inhibitors are the predominant mechanisms for other diseases, such as hepatitis, systemic lupus erythematosus and a wide range of neurodegenerative conditions. Additionally, histone deacetylase inhibitors have been shown to be efficacious in animal models of cardiac hypertrophy and asthma. Broad-spectrum histone deacetylase inhibitors are clinically available and have been used almost exclusively in preclinical systems to date. However, it is emerging that class- or isoform-specific compounds, which are becoming more readily available, may be more efficacious particularly for non-oncological applications. The aim of this review is to provide an overview of the effects and clinical potential of histone deacetylase inhibitors in various diseases. Apart from applications in oncology, the discussion is focused on the potential efficacy of histone deacetylase inhibitors for the treatment of neurodegenerative diseases, cardiac hypertrophy and asthma.
组蛋白去乙酰化酶抑制剂已成为一类新的抗癌治疗药物。它们在肿瘤学中的临床应用源于其内在的细胞毒性特性以及与其他传统癌症治疗方法的联合作用。迄今为止，组蛋白去乙酰化酶抑制剂琥珀酰亚胺羟肟酸（伏立诺他，Zolinza®）和 depsipeptide（罗米地辛，Istodax®）已被美国食品和药物管理局批准用于治疗难治性皮肤 T 细胞淋巴瘤。此外，目前有超过 100 项临床试验涉及组蛋白去乙酰化酶抑制剂在广泛的实体瘤和血液恶性肿瘤中的应用。组蛋白去乙酰化酶抑制剂的治疗潜力也已在许多其他疾病中得到研究。例如，组蛋白去乙酰化酶抑制剂的细胞毒性特性目前正被用作治疗疟疾的潜在方法，而这些化合物对 HIV 的疗效则依赖于沉默潜伏病毒。组蛋白去乙酰化酶抑制剂的抗炎特性是治疗其他疾病的主要机制，如肝炎、系统性红斑狼疮和广泛的神经退行性疾病。此外，组蛋白去乙酰化酶抑制剂已被证明在心脏肥大和哮喘的动物模型中有效。广谱组蛋白去乙酰化酶抑制剂在临床上可获得，并已在临床前系统中得到广泛应用，但目前新兴的是，具有更广泛作用的特定类别或特定亚型的化合物可能更有效，特别是在非肿瘤学应用中。本综述的目的是概述组蛋白去乙酰化酶抑制剂在各种疾病中的作用和临床潜力。除了在肿瘤学中的应用外，讨论还集中在组蛋白去乙酰化酶抑制剂治疗神经退行性疾病、心脏肥大和哮喘的潜在疗效上。
