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中华口腔医学研究杂志(电子版) ›› 2024, Vol. 18 ›› Issue (04) : 269 -275. doi: 10.3877/cma.j.issn.1674-1366.2024.04.009

综述

多聚ADP核糖聚合酶1在口腔鳞状细胞癌精准诊疗中的作用机制及转化价值
曾德荣1, 马琳2, 李星瀚2, 胡伟涛2, 刘琦3, 邓永强2,†()   
  1. 1. 深圳大学总医院口腔科，深圳　518055；深圳大学口腔医学研究所，深圳　518055；杭州师范大学口腔医学院，杭州　311121
    2. 深圳大学总医院口腔科，深圳　518055；深圳大学口腔医学研究所，深圳　518055
    3. 深圳大学口腔医学研究所，深圳　518055；深圳大学医学部国际肿瘤中心，深圳　518055
  • 收稿日期:2024-01-26 出版日期:2024-08-01
  • 通信作者: 邓永强

The importance of poly (ADP-ribose) polymerase 1 in precision medicine of oral squamous cell carcinoma

Derong Zeng1, Lin Ma2, Xinghan Li2, Weitao Hu2, Qi Liu3, Yongqiang Deng2,†()   

  1. 1. Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, China; Institute of Stomatological Research, Shenzhen University, Shenzhen 518055, China; School of Stomatology, Hangzhou Normal University, Hangzhou 311121, China
    2. Department of Stomatology, Shenzhen University General Hospital, Shenzhen University, Shenzhen 518055, China; Institute of Stomatological Research, Shenzhen University, Shenzhen 518055, China
    3. Institute of Stomatological Research, Shenzhen University, Shenzhen 518055, China; International Cancer Center, School of Medicine, Shenzhen University, Shenzhen 518055, China
  • Received:2024-01-26 Published:2024-08-01
  • Corresponding author: Yongqiang Deng
  • Supported by:
    National Natural Science Foundation of China(82073007, 82373212); Basic and Applied Basic Research Foundation of Guangdong Province(2023A1515011945)
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曾德荣, 马琳, 李星瀚, 胡伟涛, 刘琦, 邓永强. 多聚ADP核糖聚合酶1在口腔鳞状细胞癌精准诊疗中的作用机制及转化价值[J]. 中华口腔医学研究杂志(电子版), 2024, 18(04): 269-275.

Derong Zeng, Lin Ma, Xinghan Li, Weitao Hu, Qi Liu, Yongqiang Deng. The importance of poly (ADP-ribose) polymerase 1 in precision medicine of oral squamous cell carcinoma[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2024, 18(04): 269-275.

缺少有效分子靶点是阻碍口腔鳞状细胞癌（OSCC）精准诊疗进步的关键因素。多聚ADP核糖聚合酶1（PARP1）具有执行DNA损伤反应、处理氧化应激压力、抑制细胞程序性死亡等功能，是癌细胞应对生存压力的重要工具，也是适用于多种癌症治疗的分子靶点。研究显示，PARP1在OSCC诊疗中具有强大的潜力：一方面PARP1分子显像技术可用于OSCC的在体诊断，另一方面PARP抑制剂与放化疗联合应用在OSCC临床前测试中取得了良好的疗效。本文总结了PARP1在癌症治疗中的作用机制，重点阐述了PARP1应用于OSCC精准诊疗的研究进展，以促进PARP1靶点在OSCC中的临床应用转化。

关键词: 口腔肿瘤, 多聚ADP核糖聚合酶1, 多（ADP核糖）聚合酶抑制剂, 精准医学, 分子显像

The lack of effective molecular targets is a critical problem hindering the advance of precision medicine in oral squamous cell carcinoma (OSCC). Poly (ADP-ribose) polymerase 1 (PARP1) is a pleiotropic gene involved in several cellular functions, e.g., executing DNA damage response, processing oxidative stress, and inhibiting programmed cell death, making it an important tool for cancer cells to cope with survival pressures and a molecular target suitable for the treatment of various cancers. Recent research progress has shown that PARP1 has great potential in the diagnosis and treatment of OSCC. On one hand, molecular imaging techniques can be used for the in vivo diagnosis of PARP1 expression and distribution. On the other hand, the combined application of PARP inhibitors with radiochemotherapy has achieved great therapeutic effects in preclinical tests. This article summarized the mechanisms of PARP1 in cancer treatment, with a focus on elucidating the research progress in the precision medicine of OSCC using PARP1 as a molecular target, to promote the clinical application of PARP1 targeting in the treatment of OSCC.

Key words: Mouth neoplasms, Poly (ADP-ribose) polymerase 1, Poly (ADP-ribose) polymerase inhibitors, Precision medicine, Molecular imaging
图1 多聚ADP核糖聚合酶1（PARP1）蛋白结构域图解　ZN1、ZN2、ZN3：锌指结构域1、锌指结构域2、锌指结构域3；NLS：核定位信号区；BRCT：乳腺癌易感蛋白-羧基末端修饰域；WGR：富含色氨酸-甘氨酸-精氨酸域；HD：螺旋结构域；ART：ADP核糖转移酶域；ZN1、ZN3和WGR结构域协同结合DNA损伤位点，WGR结构域与ZN1、ZN3、HD、ART和DNA相互作用，是复合物的核心组分。
图2 多聚ADP核糖聚合酶1（PARP1）蛋白参与DNA损伤响应与修复　当DNA发生损伤，PARP1蛋白识别DNA损伤并结合于损伤位点，以β-烟酰胺腺嘌呤二核苷酸（NAD+）和ATP为底物，生成烟酰胺（NAM）和ADP核糖，ADP核糖与PARP1或其他DNA修复蛋白结合，进行多聚ADP-核糖基化修饰，参与修复碱基损伤、核苷酸损伤、DNA单链断裂和双链断裂。
图3 阻断多聚ADP核糖聚合酶1（PARP1）与同源重组（HR）修复途径诱导细胞合成致死效应图解　A：正常细胞出现DNA损伤时可通过2种主要DNA损伤修复途径PARP1和HR来修复DNA损伤，细胞得以存活；B：正常细胞的PARP1修复途径被药物阻断，HR修复途径发挥主要DNA损伤修复功能，细胞存活；C：正常细胞HR修复途径受损，PARP1修复途径发挥主要DNA损伤修复功能，细胞存活；D：当细胞的2条主要DNA损伤修复通路同时受损，DNA损伤无法及时被修复，细胞最终死亡。
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