癌症进展除了基因改变外，还受到表观遗传事件的强烈影响。在基因表达的表观遗传调控中，组蛋白修饰通过醋酸化起到关键作用，这种修饰由组蛋白乙酰转移酶 (HATs) 和组蛋白去乙酰酶 (HDACs) 协同调控。HDAC被认为在癌症药物开发中具有可观的潜力，特别是与其他抗癌药物和/或放疗联合使用时。血栓强化剂 (Beleodaq, PXD101) 是一种带有磺胺基团的全HDAC非饱和羟胺酸酯抑制剂，已被美国食品药品监督管理局 (FDA) 批准用于难治性或复发的外周T细胞淋巴瘤 (PTCL) 以及实体肿瘤和其他血液组织治疗。该药物修饰组蛋白和表观遗传途径。由于HDAC和HAT不平衡可能导致调控基因的下调，从而导致肿瘤发生。Belinostat通过抑制HDAC间接促进抗癌治疗效果，通过促进乙酰化组蛋白积累，在癌细胞中重新建立正常基因表达，并刺激免疫应答、p27信号级联、Caspase 3激活、核蛋白多聚(ADP核糖)聚合酶-1 (PARP-1) 降解、细胞周期蛋白 A (G2/M期) 和细胞周期蛋白 E1 (G1/S期) 等途径。此外，Belinostat还被发现在多种细胞系(黑色素瘤、前列腺、乳腺、肺、结肠和卵巢)中能促进p21WAF1的表达。这种细胞周期依赖性激酶抑制剂在引起细胞周期阻滞和凋亡的过程中发挥作用。Belinostat在实体和血液肿瘤领域的临床有效性已通过多个研究试验得到证明，支持其成为一种有价值的抗癌药物的潜力。本研究的目的是提供对Belinostat抑制HDAC的具体分子过程的深入了解。通过对这些特定途径的更好理解，有望探索新的靶向治疗选项，并对癌细胞异常有更深入的了解。版权所有 © 2023作者。由 Elsevier Masson SAS出版。保留所有权利。

Cancer progression is strongly affected by epigenetic events in addition to genetic modifications. One of the key elements in the epigenetic control of gene expression is histone modification through acetylation, which is regulated by the synergy between histone acetyltransferases (HATs) and histone deacetylases (HDACs). HDACs are thought to offer considerable potential for the development of anticancer medications, particularly when used in conjunction with other anticancer medications and/or radiotherapy. Belinostat (Beleodaq, PXD101) is a pan-HDAC unsaturated hydroxamate inhibitor with a sulfonamide group that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of refractory or relapsed peripheral T-cell lymphoma (PTCL) and solid malignancies or and other hematological tissues. This drug modifies histones and epigenetic pathways. Because HDAC and HAT imbalance can lead to downregulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by belinostat indirectly promotes anti-cancer therapeutic effect by provoking acetylated histone accumulation, re-establishing normal gene expressions in cancer cells and stimulating other routes such as the immune response, p27 signaling cascades, caspase 3 activation, nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) degradation, cyclin A (G2/M phase), cyclin E1 (G1/S phase) and other events. In addition, belinostat has already been discovered to increase p21WAF1 in a number of cell lines (melanoma, prostate, breast, lung, colon, and ovary). This cyclin-dependent kinase inhibitor actually has a role in processes that cause cell cycle arrest and apoptosis. Belinostat's clinical effectiveness, comprising Phase I and II studies within the areas of solid and hematological cancers, has been evidenced through several investigative trials that have supported its potential to be a valuable anti-cancer drug. The purpose of this research was to provide insight on the specific molecular processes through which belinostat inhibits HDAC. The ability to investigate new therapeutic options employing targeted therapy and acquire a deeper understanding of cancer cell abnormalities may result from a better understanding of these particular routes.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.