School of Health & Medicine, Division of Biomedical & Life Sciences, Lancaster University, Lancaster LA14YQ, UK.
Future Oncol. 2010 Jun;6(6):1031-42. doi: 10.2217/fon.10.40.
Pharmacological inhibition of DNA-repair pathways as an approach for the potentiation of chemo- and radio-therapeutic cancer treatments has attracted increasing levels of interest in recent years. Inhibitors of several enzymes involved in the repair of DNA strand breaks are currently at various stages of the drug development process. Polynucleotide kinase (PNK), a bifunctional DNA-repair enzyme that possesses both 3'-phosphatase and 5'-kinase activities, plays an important role in the repair of both single strand and double strand breaks and as a result, RNAi-mediated knockdown of PNK sensitizes cells to a range of DNA-damaging agents. Recently, a small molecule inhibitor of PNK has been developed that is able to sensitize cells to ionizing radiation and the topoisomerase I poison, camptothecin. Although still in the early stages of development, PNK inhibition represents a promising means of enhancing the efficacy of existing cancer treatments.
近年来，抑制 DNA 修复途径的药理学方法作为增强化疗和放疗癌症治疗效果的一种手段引起了越来越多的关注。目前，有几种参与 DNA 链断裂修复的酶抑制剂处于药物开发过程的不同阶段。多核苷酸激酶（PNK）是一种具有 3'-磷酸酶和 5'-激酶活性的双功能 DNA 修复酶，在单链和双链断裂的修复中起着重要作用，因此，PNK 的 RNAi 介导的敲低使细胞对多种 DNA 损伤剂敏感。最近，开发了一种 PNK 的小分子抑制剂，它能够使细胞对电离辐射和拓扑异构酶 I 毒物喜树碱敏感。尽管仍处于早期开发阶段，但 PNK 抑制代表了增强现有癌症治疗效果的一种有前途的手段。
