Chen I-Chung, Sethy Bidyadhar, Liou Jing-Ping
School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Front Cell Dev Biol. 2020 Sep 3;8:576391. doi: 10.3389/fcell.2020.576391. eCollection 2020.
Modulating epigenetic modification has been recognized for over a decade as an effective therapeutic approach to cancer and many studies of histone deacetylase (HDAC), one of the best known epigenetic modulators, have been published. HDAC modulates cell proliferation and angiogenesis and plays an essential role in cell growth. Research shows that up-regulated HDACs are present in many cancer types and synthetic or natural HDAC inhibitors have been used to silence overregulated HDACs. Inhibiting HDACs may cause arrest of cell proliferation, angiogenesis reduction and cell apoptosis. Recent studies indicate that HDAC inhibitors can provide a therapeutic effect in various cancers, such as B-cell lymphoma, leukemia, multiple myeloma and some virus-associated cancers. Some evidence has demonstrated that HDAC inhibitors can increase the expression of immune-related molecules leading to accumulation of CD8 + T cells and causing unresponsive tumor cells to be recognized by the immune system, reducing tumor immunity. This may be a solution for the blockade of PD-1. Here, we review the emerging development of HDAC inhibitors in various cancer treatments and reduction of tumor immunity.
十多年来,调节表观遗传修饰已被公认为是一种有效的癌症治疗方法,并且已经发表了许多关于组蛋白脱乙酰酶(HDAC)的研究,HDAC是最著名的表观遗传调节剂之一。HDAC调节细胞增殖和血管生成,并在细胞生长中起重要作用。研究表明,许多癌症类型中都存在上调的HDAC,并且已使用合成或天然的HDAC抑制剂来沉默过度上调的HDAC。抑制HDAC可能导致细胞增殖停滞、血管生成减少和细胞凋亡。最近的研究表明,HDAC抑制剂可以在各种癌症中提供治疗效果,例如B细胞淋巴瘤、白血病、多发性骨髓瘤和一些病毒相关癌症。一些证据表明,HDAC抑制剂可以增加免疫相关分子的表达,导致CD8 + T细胞积累,并使无反应的肿瘤细胞被免疫系统识别,从而降低肿瘤免疫。这可能是解决PD-1阻断的一种方法。在这里,我们综述了HDAC抑制剂在各种癌症治疗和降低肿瘤免疫方面的新进展。