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首页> 外文期刊>Gene Therapy and Molecular Biology >Histone deacetylase inhibitors: promisingcandidates for chemotherapeutic drugs
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Histone deacetylase inhibitors: promisingcandidates for chemotherapeutic drugs

机译：组蛋白脱乙酰基酶抑制剂：化学治疗药物的有前途的候选人

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Despite advances in the molecular understanding of tumorigenesis and tumor cell apoptosis, the efficacy of chemotherapeutic treatment has not significantly improved over the last decades. Conventional treatment regimens suffer from a small therapeutic window and are often associated with severe side effects. Recent data suggest that a novel class of compounds, the histone deacetylase inhibitors (HDAC inhibitors), displays potent cytotoxicity towards tumor cells with low or negligible effects on untransformed cells. In addition to causing cell cycle arrest and/or differentiation and programmed cell death in tumor cells, they can also inhibit tumor angiogenesis and display immunosuppressive properties. Excitingly, various HDAC inhibitors compounds show synergy with other anti- cancer drugs and are involved in early clinical trials or pre-clinical development.The mechanism of action of HDAC inhibitors has not been completely elucidated. They induce histone hyperacetylation associated with transcriptional modulation of a set of genes. Treatment of malignant cells with HDAC inhibitors has been reported to elicit upregulation of the cell cycle inhibitor p21(WAF1), and induction of apoptosis most likely is coincident with the cleavage and activation of the proapoptotic Bcl-2 family member Bid. In addition, reactive oxygen species seem to play an important role in HDAC inhibitor-mediated cell death.This article summarizes what is currently known about the molecular and systemic sequelae of HDAC inhibitor treatment and focuses on recent progress regardingpotential applications for cancer treatment as stand-alone or combination therapy.
机译：尽管在肿瘤发生和肿瘤细胞凋亡的分子理解上取得了进步，但化学治疗的效果在过去的几十年中并未得到明显改善。常规治疗方案具有小的治疗窗口，并且经常与严重的副作用有关。最近的数据表明，一类新型的化合物，组蛋白脱乙酰基酶抑制剂（HDAC抑制剂），对肿瘤细胞表现出强力的细胞毒性，对未转化的细胞的影响很小或可忽略不计。除了在肿瘤细胞中引起细胞周期停滞和/或分化以及程序性细胞死亡外，它们还可以抑制肿瘤血管生成并显示免疫抑制特性。令人兴奋的是，各种HDAC抑制剂化合物显示出与其他抗癌药物的协同作用，并参与了早期临床试验或临床前开发。HDAC抑制剂的作用机理尚未完全阐明。它们诱导与一组基因的转录调节相关的组蛋白超乙酰化。已有报道称用HDAC抑制剂治疗恶性细胞会引起细胞周期抑制剂p21（WAF1）的上调，并且诱导凋亡最可能与促凋亡Bcl-2家族成员Bid的裂解和激活同时发生。另外，活性氧似乎在HDAC抑制剂介导的细胞死亡中起着重要作用。单独或联合治疗。

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