Miller Claudia P, Singh Melissa M, Rivera-Del Valle Nilsa, Manton Christa A, Chandra Joya
Department of Pediatrics Research, Children's Cancer Hospital, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
J Biomed Biotechnol. 2011;2011:514261. doi: 10.1155/2011/514261. Epub 2011 Jun 28.
Histone acetylation is a posttranslational modification that plays a role in regulating gene expression. More recently, other nonhistone proteins have been identified to be acetylated which can regulate their function, stability, localization, or interaction with other molecules. Modulating acetylation with histone deacetylase inhibitors (HDACi) has been validated to have anticancer effects in preclinical and clinical cancer models. This has led to development and approval of the first HDACi, vorinostat, for the treatment of cutaneous T cell lymphoma. However, to date, targeting acetylation with HDACi as a monotherapy has shown modest activity against other cancers. To improve their efficacy, HDACi have been paired with other antitumor agents. Here, we discuss several combination therapies, highlighting various epigenetic drugs, ROS-generating agents, proteasome inhibitors, and DNA-damaging compounds that together may provide a therapeutic advantage over single-agent strategies.
组蛋白乙酰化是一种翻译后修饰，在调节基因表达中发挥作用。最近，已鉴定出其他非组蛋白蛋白质也会发生乙酰化，这可调节它们的功能、稳定性、定位或与其他分子的相互作用。在临床前和临床癌症模型中，用组蛋白去乙酰化酶抑制剂（HDACi）调节乙酰化已被证实具有抗癌作用。这导致了首个HDACi伏立诺他的研发和批准，用于治疗皮肤T细胞淋巴瘤。然而，迄今为止，将HDACi作为单一疗法靶向乙酰化对其他癌症的活性一直较为有限。为提高其疗效，HDACi已与其他抗肿瘤药物联合使用。在此，我们讨论几种联合疗法，重点介绍各种表观遗传药物、活性氧生成剂、蛋白酶体抑制剂和DNA损伤化合物，它们共同作用可能比单一药物策略具有治疗优势。
