Hitting the Bull's Eye: Novel Directed Cancer Therapy Through Helicase-Targeted Synthetic Lethality
Hitting the Bull's Eye: Novel Directed Cancer Therapy Through Helicase-Targeted Synthetic Lethality
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DOI：
10.1002/jcb.22048
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发表时间：
2009-04-01
影响因子：
4
通讯作者：
Brosh, Robert M., Jr.
中科院分区：
文献类型：
--
作者：
Aggarwal, Monika;Brosh, Robert M., Jr.
设计抗癌治疗策略提出了重大挑战。一种方法是抑制特定的 DNA 修复蛋白及其各自的途径，以增强用于治疗癌症患者的化疗和放疗。合成致死代表了一种利用某些肿瘤中预先存在的 DNA 修复缺陷来开发 DNA 修复途径抑制剂来补偿肿瘤相关修复缺陷的方法。由于解旋酶在 DNA 损伤反应和 DNA 修复中发挥着关键作用，特别是在活跃分裂和复制的细胞中，因此提出 DNA 解旋酶合成致死关系的鉴定和表征对于开发改进的抗癌治疗策略具有重要价值。在这篇综述中，我们讨论了模型系统中真核 DNA 解旋酶合成致死相互作用的这一假设和当前证据。 J.细胞。生物化学。 106: 758-763, 2009。2009 年出版 Wiley-Liss, Inc.
Designing strategies for anti-cancer therapy have posed a significant challenge. One approach has been to inhibit specific DNA repair proteins and their respective pathways to enhance chemotherapy and radiation therapy used to treat cancer patients. Synthetic lethality represents an approach that exploits pre-existing DNA repair deficiencies in certain tumors to develop inhibitors of DNA repair pathways that compensate for the tumor-associated repair deficiency. Since helicases play critical roles in the DNA damage response and DNA repair, particularly in actively dividing and replicating cells, it is proposed that the identification and characterization of synthetic lethal relationships of DNA helicases will be of value in developing improved anti-cancer treatment strategies. In this review, we discuss this hypothesis and current evidence for synthetic lethal interactions of eukaryotic DNA helicases in model systems. J. Cell. Biochem. 106: 758-763, 2009. Published 2009 Wiley-Liss, Inc.