Northern Institute for Cancer Research, Newcastle University, Paul O'Gorman Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
Breast Cancer Res. 2011 Aug 16;13(4):218. doi: 10.1186/bcr2877.
Inhibitors of poly(ADP-ribose) polymerase (PARP)-mediated DNA repair have shown promise in early clinical studies in the treatment of specific subgroups of breast cancer. Notably, phase II trials indicate that olaparib, an oral PARP inhibitor, has activity as a single agent in BRCA-related tumours, and that a combination of iniparib, an intravenous PARP inhibitor, and chemotherapy offers a survival advantage, compared with chemotherapy alone, in triple-negative breast cancer. Phase III data on the latter indication are expected in 2011. Intriguingly, iniparib does not increase toxicity when used as a chemo-potentiating agent, suggesting that it differs in its mechanism of action from other agents in this class. Overall, PARP inhibitors represent a potentially important new class of anti-cancer agents with two potential modes of action, as single agents causing synthetic lethality and as chemo-potentiating agents.
聚（ADP-核糖）聚合酶（PARP）介导的 DNA 修复抑制剂在特定亚组乳腺癌的早期临床研究中显示出良好的前景。值得注意的是，II 期试验表明，口服 PARP 抑制剂奥拉帕尼在 BRCA 相关肿瘤中作为单一药物具有活性，而静脉注射 PARP 抑制剂尼拉帕尼与化疗联合使用与单独化疗相比，在三阴性乳腺癌中具有生存优势。关于后一种适应症的 III 期数据预计将于 2011 年公布。有趣的是，尼拉帕尼作为化疗增敏剂使用时不会增加毒性，这表明它与该类别的其他药物在作用机制上有所不同。总体而言，PARP 抑制剂代表了一类具有两种潜在作用模式的潜在重要新型抗癌药物，作为单一药物引起合成致死性，作为化疗增敏剂。
