School of Medicine, Baylor College of Medicine, Houston, TX, USA.
Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Expert Opin Ther Targets. 2021 Nov;25(11):1025-1026. doi: 10.1080/14728222.2021.2010189. Epub 2021 Dec 3.
Cutaneous squamous cell carcinoma (cSCC) is the second most common malignancy; as such, novel systemic therapies are important for the treatment of locally advanced or metastatic disease. Histone deacetylase (HDAC) inhibitors have been increasingly studied in recent years as epigenome-targeted therapy for cSCC. HDACs inhibitors reduce tumorigenesis by blocking HDAC activity and creating a more relaxed chromatin structure, thus inducing gene expression by inhibiting deacetylation of transcription factors. In vitro experiments and in vivo mice studies have shown that HDAC inhibition halts cSCC pathogenesis. Ginsenoside 20(R)-Rg3 has been successfully employed to inhibit HDAC3 and thereby inhibit cSCC epithelial mesenchymal transition. Similarly, vorinostat has been found to blunt growth of human xenograft epidermoid cSCCs in highly immunosuppressed mice. Additionally, trichostatin A induces irreversible growth arrest in SCC cells, and MS-275 significantly reduces cSCC tumor burden in mice. These recent studies indicate that HDAC inhibitors represent a promising emerging therapy for cSCC.
皮肤鳞状细胞癌（cSCC）是第二大常见恶性肿瘤；因此，新型系统疗法对于局部晚期或转移性疾病的治疗非常重要。近年来，组蛋白去乙酰化酶（HDAC）抑制剂作为 cSCC 的表观基因组靶向治疗越来越受到关注。HDAC 抑制剂通过阻断 HDAC 活性并创造更松弛的染色质结构来减少肿瘤发生，从而通过抑制转录因子的去乙酰化来诱导基因表达。体外实验和体内小鼠研究表明，HDAC 抑制可阻止 cSCC 的发病机制。人参皂苷 20(R)-Rg3 已成功用于抑制 HDAC3，从而抑制 cSCC 上皮间质转化。同样，伏立诺他已被发现可阻止高免疫抑制小鼠中人类异种移植物表皮鳞癌 cSCC 的生长。此外，曲古抑菌素 A 可诱导 SCC 细胞不可逆的生长停滞，MS-275 可显著减少小鼠的 cSCC 肿瘤负担。这些最新研究表明，HDAC 抑制剂代表了 cSCC 一种有前途的新兴治疗方法。
