Parveen Roza, Harihar Divya, Chatterji Biswa Prasun
Faculty of Medicine and Health Sciences, Tampere University, Tampere, Finland.
School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
Cancer. 2023 Nov 1;129(21):3372-3380. doi: 10.1002/cncr.34974. Epub 2023 Aug 10.
Cancer metastasis increases the complexity of the disease and escalates patient mortality. Traditional chemotherapy has been associated with low efficacy and marked side effects. Studies pivot toward histone deacetylase (HDAC) enzymes and inhibitors because they are critical for chromatin structure, gene regulation, and cellular activities that are linked to metastasis and cancer progression. HDAC inhibitors (HDACi) can alter gene expression patterns and can lead to cell-cycle arrest and apoptosis in neoplastic cells. Several HDACi drugs like vorinostat, romidepsin, panobinostat, and belinostat are approved by the Food and Drug Administration. China and Japan have approved the use of tucidinostat, a new subtype-selective HDACi that inhibits class 1 HDAC1, HDAC2, HDAC3, as well as class 2b HDAC10. These drugs have shown promising results in the treatment of multiple carcinoma including cervical cancer, T-cell lymphoma, brain cancer, and breast cancer. This review highlights the HDACi classes, the mechanism of action of these inhibitors, their preclinical and clinical efficacy, and the latest clinical trials and patents used in cancer therapeutics. Overall, this review focuses on patents and clinical trials data from 2019 onward to give a better viewpoint on current trends in HDACis as chemotherapy agents.
癌症转移增加了疾病的复杂性并提高了患者死亡率。传统化疗疗效低且副作用明显。研究转向组蛋白去乙酰化酶(HDAC)及其抑制剂,因为它们对染色质结构、基因调控以及与转移和癌症进展相关的细胞活动至关重要。HDAC抑制剂(HDACi)可改变基因表达模式,并可导致肿瘤细胞的细胞周期停滞和凋亡。几种HDACi药物,如伏立诺他、罗米地辛、帕比司他和贝利司他已获美国食品药品监督管理局批准。中国和日本已批准使用图西诺司他,这是一种新型亚型选择性HDACi,可抑制1类HDAC1、HDAC2、HDAC3以及2b类HDAC10。这些药物在治疗多种癌症(包括宫颈癌、T细胞淋巴瘤、脑癌和乳腺癌)方面已显示出有前景的结果。本综述重点介绍了HDACi的类别、这些抑制剂的作用机制、它们的临床前和临床疗效,以及癌症治疗中使用的最新临床试验和专利。总体而言,本综述重点关注2019年以来的专利和临床试验数据,以便更好地了解HDACi作为化疗药物的当前趋势。