Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon 24341, Korea.
Int J Mol Sci. 2022 Aug 24;23(17):9592. doi: 10.3390/ijms23179592.
Histone deacetylases (HDACs) regulate gene expression through the epigenetic modification of chromatin structure. HDAC6, unlike many other HDACs, is present in the cytoplasm. Its deacetylates non-histone proteins and plays diverse roles in cancer cell initiation, proliferation, autophagy, and anti-cancer drug resistance. The development of HDAC6-specific inhibitors has been relatively successful. Mechanisms of HDAC6-promoted anti-cancer drug resistance, cancer cell proliferation, and autophagy are discussed. The relationship between autophagy and anti-cancer drug resistance is discussed. The effects of combination therapy, which includes HDAC6 inhibitors, on the sensitivity of cancer cells to chemotherapeutics and immune checkpoint blockade are presented. A summary of clinical trials involving HDAC6-specific inhibitors is also presented. This review presents HDAC6 as a valuable target for developing anti-cancer drugs.
组蛋白去乙酰化酶（HDACs）通过对染色质结构的表观遗传修饰来调节基因表达。与许多其他 HDAC 不同，HDAC6 存在于细胞质中。它去乙酰化非组蛋白蛋白，并在癌细胞起始、增殖、自噬和抗癌药物耐药性中发挥多种作用。HDAC6 特异性抑制剂的开发相对较为成功。讨论了 HDAC6 促进抗癌药物耐药性、癌细胞增殖和自噬的机制。讨论了自噬与抗癌药物耐药性的关系。介绍了包括 HDAC6 抑制剂在内的联合治疗对癌细胞对化疗药物和免疫检查点阻断的敏感性的影响。还介绍了涉及 HDAC6 特异性抑制剂的临床试验的总结。本综述将 HDAC6 视为开发抗癌药物的有价值的靶标。
