In response to a variety of cellular stresses, poly(ADP-ribose) polymerase 1 (PARP1) has vital roles in orchestrating DNA damage repair and preserving genomic integrity. Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leading to clinical approval of several PARPis. Preclinical and clinical studies aiming to broaden the therapeutic application of PARPis identified sensitivity biomarkers and rationale combination strategies that can target BRCA wild-type and homologous recombination (HR) DNA repair-proficient cancers, including central nervous system (CNS) malignancies. In this review, we summarize recent progress in PARPi therapy in brain tumors, and discuss current opportunities for, and challenges to, the use of PARPis in neuro-oncology.

响应各种细胞应激，聚（ADP-核糖）聚合酶1（PARP1）在协调DNA损伤修复和保持基因组完整性方面起着至关重要的作用。在BRCA1 / 2突变型癌症中，PARP抑制剂（PARPis）的临床活性验证了PARP抑制与有害BRCA1 / 2突变之间的合成致死性概念，从而导致了几种PARPis的临床批准。旨在扩大PARP的治疗应用的临床前和临床研究确定了可针对BRCA野生型和同源重组（HR）DNA修复能力强的癌症（包括中枢神经系统（CNS）恶性肿瘤）的敏感性生物标志物和基本原理联合策略。在这篇综述中，我们总结了PARPi治疗脑肿瘤的最新进展，并讨论了当前的机会和挑战，