| 摘要: |
| 细胞修复DNA损伤的能力与肿瘤的发生发展及治疗效果密切相关。肿瘤治疗中广泛使用的DNA损伤药物和放射治疗都会造成DNA双链断裂这种致命性的损伤，肿瘤细胞主要通过 DNA依赖性蛋白激酶（DNA-PK）参与的一种非同源末端连接（NHEJ）方式来进行修复。DNA-PK全酶由催化亚单位DNA-PKcs和Ku70/Ku80异二聚体两部分组成，对它们活性的抑制能显著降低肿瘤细胞修复DNA双链断裂的能力，进而增强放化疗的敏感性。目前研究主要关注DNA-PKcs抑制剂，其中一些已进入临床研究阶段。本文对多种DNA-PKcs抑制剂在肿瘤治疗中的相关研究进行概括。 |
| 关键词: DNA-PKcs抑制剂 肿瘤 放射疗法 化学疗法 敏感性 |
| DOI：10.11724/jdmu.2018.05.01 |
| 分类号:R737. 33 |
| 基金项目:基金项目：国家自然科学基金项目（81611130075）; 辽宁省自然科学基金联合基金项目（20180530070） |
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| Research status of DNA-PKcs inhibitors in therapy of cancer |
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WANG Aoxue1, MA Jingxin2
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1.Department of Dermatology, the Second Affiliated Hospital of Dalian Medical University, Dalian 116027,China;2.Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China
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| Abstract: |
| The capability of a cell to repair the DNA damage was tightly associated with the development and therapeutic effect of cancer. DNA damaging drugs and radiotherapy widely used in tumor treatment cause a lethal lesion-DNA double-strand break (DSBs), which are repaired mainly by non-homologous-end-joining (NHEJ). DNA-dependent protein kinase (DNA-PK) plays key roles in NHEJ and is composed of a catalytic subunit DNA-PKcs and a heterodimeric subunit Ku70/Ku80. Suppressing the activities of these two components can attenuate the repairmetn of DSBs and enhance the sensitivities of tumor cells against chemotherapy and radiotherapy. Nowadays, studies mainly focus on DNA-PKcs inhibitors, some of which have entered clinical trial. In this mini-review, progresses on DNA-PKcs inhibitors in tumor therapy have been summarized. |
| Key words: DNA-PKcs inhibitors tumour radiation therapy chemotherapy sensibility |
