PARP inhibitors for anticancer therapy
PARP inhibitors for anticancer therapy
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DOI：
10.1042/bst20130187
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发表时间：
2014-02-01
影响因子：
3.9
通讯作者：
Curtin, Nicola
中科院分区：
文献类型：
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作者：
Curtin, Nicola
PARP-1[聚（adp -核糖）聚合酶1]在DNA修复中起关键作用，于50年前被发现。PARPi （PARP抑制剂），最初用于探测酶的功能，抑制DNA修复并增加抗癌细胞毒性药物的效力。效价越来越高的PARPi被开发为化疗和放射增敏剂，并于2003年首次进入癌症患者的临床试验。然而，2005年发现它们在具有DNA修复缺陷的细胞中具有合成致命性，这种缺陷几乎只在某些肿瘤中发现，这引起了人们对这类药物的主要兴趣。一些PARPi已经进入临床试验，并在乳腺癌、卵巢癌和其他与BRCA（乳腺癌早发性）突变或其他同源重组DNA修复缺陷相关的癌症中显示出有希望的活性。很可能其中至少有一种将很快获得许可。本文综述了PARPi从发现到临床应用的关键事件。
PARP-1 [poly(ADP-ribose) polymerase-1], which plays a key role in DNA repair, was discovered 50 years ago. PARPi (PARP inhibitors), originally made to probe the function of the enzyme, inhibit DNA repair and increase the potency of anticancer cytotoxic agents. PARPi of increasing potency were developed as chemo- and radio-sensitizers and first entered clinical trial in cancer patients in 2003. However, it was the revelation in 2005 that they were synthetically lethal in cells with DNA repair defects, found almost exclusively in some tumours, that led to a major interest in this class of drug. Several PARPi have entered clinical trials and show promising activity in breast, ovarian and other cancers associated with BRCA (breast cancer early-onset) mutations or other defects in homologous recombination DNA repair. It is likely that at least one of these will be licensed soon. The present review describes key events from the discovery to clinical application of PARPi.