聚腺苷二磷酸核糖聚合酶抑制剂在肿瘤放射治疗中的应用研究进展

Progress in the application of poly ADP-ribose polymerase inhibitors in tumor radiotherapy

聚腺苷二磷酸核糖聚合酶(PARP)是一类在真核细胞中高表达的核酶,在DNA损伤修复中起关键作用。近年来,PARP抑制剂在肿瘤治疗中显示出巨大的潜力,几种小分子PARP抑制剂已被美国食品药品管理局(FDA)批准用于多种肿瘤的维持治疗。PARP抑制剂主要通过抑制PARP酶促作用和PARP捕获作用,导致DNA单链断裂的持续存在,在DNA复制的过程中,转变为双链断裂。研究证明,PARP抑制剂不仅具有显著的抗肿瘤效应,而且与放射治疗联合具有一定的协同作用。本文将阐述PARP抑制剂联合放疗的潜在理论基础,总结近年来PARP抑制剂在肿瘤放射治疗中的临床前和临床研究进展,梳理该领域目前亟待解决的问题,并对其在抗肿瘤治疗中的应用前景进行展望。

The poly ADP-ribose polymerase(PARP)is a class of nuclear enzymes highly expressed in eukaryotic cells and plays a key role in DNA damage repair.In recent years,PARP inhibitors have shown great potential in tumor therapy,and several PARP inhibitors have been approved by the FDA for maintenance therapy of a variety of cancers.PARP inhibitors mainly inhibit PARP enzymes and PARP trapping,resulting in the persistence of DNA single strand breaks,which are converted to double strand breaks during DNA replication.Studies have shown that PARP inhibitors not only have a significant anti-tumor effect,but also have a synergistic effect with radiotherapy.This paper reviewed the potential theoretical basis of PARP inhibitor combined with radiotherapy,summarized the recent progress of preclinical and clinical research on PARP inhibitors in tumor radiotherapy,sorted out the urgent problems in this field,and looked into the application prospect of PARP inhibitors in anti-tumor therapy.