Grabarska Aneta, Dmoszyńska-Graniczka Magdalena, Nowosadzka Ewa, Stepulak Andrzej
Katedra i Zakład Biochemii i Biologii Molekularnej Uniwersytetu Medycznego w Lublinie.
Postepy Hig Med Dosw (Online). 2013 Aug 2;67:722-35. doi: 10.5604/17322693.1061381.
Histone deacetylases (HDACs) play an important role in the epigenetic regulation of gene expression implicated in cancer pathogenesis. Inhibitors of HDACs (HDI) are under investigation as novel anti-cancer drugs, which induce histone hyperacetylation. These agents modulate chromatin structure leading to transcriptional changes of a very large number of genes, which affect signaling pathways, inhibit cell cycle progression and angiogenesis, and induce apoptosis in cancer cells. Currently, several HDI are in clinical trials used in monotherapy or in combination with other cytostatics, showing promising anticancer effects. To date, more than 15 HDIs have been found as potential drugs. This paper reviews the molecular mechanisms of HDI action on cancer cells and summarizes clinical trials of the most promising HDIs in the treatment of patients with hematologic malignancies and solid tumors.
组蛋白去乙酰化酶(HDACs)在涉及癌症发病机制的基因表达表观遗传调控中发挥着重要作用。HDACs抑制剂(HDI)作为新型抗癌药物正在研究中,其可诱导组蛋白高度乙酰化。这些药物调节染色质结构,导致大量基因的转录变化,影响信号通路,抑制细胞周期进程和血管生成,并诱导癌细胞凋亡。目前,几种HDI正在进行临床试验,用于单一疗法或与其他细胞抑制剂联合使用,显示出有前景的抗癌效果。迄今为止,已发现超过15种HDI作为潜在药物。本文综述了HDI对癌细胞作用的分子机制,并总结了最有前景的HDI在治疗血液系统恶性肿瘤和实体瘤患者方面的临床试验情况。