Targeting DNA repair pathways: a novel approach to reduce cancer therapeutic resistance.
Targeting DNA repair pathways: a novel approach to reduce cancer therapeutic resistance.
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DOI：
10.1016/j.ctrv.2009.06.005
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发表时间：
2009-11
影响因子：
11.8
通讯作者：
Yongjian Zhu;Jue Hu;Yiduo Hu;Wei-guo Liu
中科院分区：
文献类型：
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作者：
Yongjian Zhu;Jue Hu;Yiduo Hu;Wei-guo Liu
癌细胞的化学抗性和放射抗性增加是恶性癌症治疗和管理的主要障碍。形成这种治疗耐药性的一个重要机制是癌细胞识别由 DNA 损伤剂和电离辐射诱导的 DNA 损伤，并通过激活各种 DNA 修复途径来修复这些损伤。因此，使用能够抑制癌细胞中某些DNA修复途径的药物有可能增强抗癌治疗的靶向细胞毒性，并逆转与DNA修复相关的治疗耐药性；此类药物为实现更好的治疗效果提供了有希望的机会。在这里，我们回顾了主要的 DNA 修复途径，并讨论了新型 DNA 修复途径抑制剂开发的最新进展；其中许多药物正在进行临床前/临床研究。
Increased chemo-resistance and radio-resistance of cancer cells is a major obstacle in the treatment and management of malignant cancers. An important mechanism that underlies the development of such therapeutic resistance is that cancer cells recognize DNA lesions induced by DNA-damaging agents and by ionizing radiation, and repair these lesions by activating various DNA repair pathways. Therefore, Use of pharmacological agents that can inhibit certain DNA repair pathways in cancer cells has the potential for enhancing the targeted cytotoxicity of anticancer treatments and reversing the associated therapeutic resistance associated with DNA repair; such agents, offering a promising opportunity to achieve better therapeutic efficacy. Here we review the major DNA repair pathways and discuss recent advances in the development of novel inhibitors of DNA repair pathways; many of these agents are under preclinical/clinical investigation.