Rational Combinations Using HDAC Inhibitors
Rational Combinations Using HDAC Inhibitors
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DOI：
10.1158/1078-0432.ccr-08-2786
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发表时间：
2009-06-15
影响因子：
11.5
通讯作者：
Johnstone, Ricky W.
中科院分区：
文献类型：
--
作者：
Bots, Michael;Johnstone, Ricky W.
除了导致癌症发生和发展的特征明确的遗传异常外，现在人们认识到，表观基因组的改变也可能在肿瘤发生中发挥重要作用。因此，组蛋白脱乙酰酶抑制剂(HDACi)等表观遗传调节剂作为抗癌药物引起了人们极大的关注。在众多的体外和临床前环境中，这些化合物已经显示出作为单药抗癌治疗的巨大潜力，但不幸的是，在患者身上并不总是观察到同等的反应。鉴于HDACi对恶性肿瘤细胞具有多效性，其真正的治疗潜力很可能在于与其他抗癌药物的联合使用。在这篇综述中，我们将集中于HDACi与其他癌症治疗药物联合使用时的抗癌作用，重点是那些基于强大分子基础的联合治疗。
In addition to well-characterized genetic abnormalities that lead to cancer onset and progression, it is now recognized that alterations to the epigenome may also play a significant role in oncogenesis. As a result, epigenetic-modulating agents such as histone deacetylase inhibitors (HDACi) have attracted enormous attention as anticancer drugs. In numerous in vitro and preclinical settings, these compounds have shown their vast potential as single agent anticancer therapies, but unfortunately equivalent responses have not always been observed in patients. Given the pleiotropic effects HDACi have on malignant cells, their true therapeutic potential most likely lies in combination with other anticancer drugs. In this review we will focus on the anticancer effects of HDACi when combined with other cancer therapeutics with an emphasis on those combinations based on a strong molecular rationale.