靶向聚（ADP-核糖）聚合酶（PARP）蛋白已显示出对 BRCA 突变导致的同源重组（HR）缺陷癌症的治疗功效。只有一小部分急性髓系白血病 (AML) 细胞携带 BRCA 突变，因此 PARP 抑制剂 (PARPi) 对这种恶性肿瘤的抗肿瘤功效预计有限；然而，最近的临床前研究表明，PARPi单药治疗对AML疗效有限，而与细胞毒性化疗联合使用则具有显着的协同抗肿瘤作用。免疫疗法彻底改变了癌症治疗的疗法，而 PARPi 通过促进肿瘤突变负荷为免疫调节剂联合治疗创造了理想的微环境。在这篇综述中，我们总结了 PARP 蛋白在 DNA 损伤反应 (DDR) 途径中的作用，并讨论了最近使用合成致死方式治疗 AML 的临床前研究。我们还回顾了 PARPi 在 AML 临床前模型中的免疫调节作用，并提出了 AML 治疗的未来方向，包括联合靶向 DDR 和肿瘤免疫微环境；这种联合方案可能会使接受 PARPi 介导的癌症治疗的 AML 患者受益。版权所有 © 2024 Bian、Liu、Yang 和 Sun。

Targeting the poly (ADP-ribose) polymerase (PARP) protein has shown therapeutic efficacy in cancers with homologous recombination (HR) deficiency due to BRCA mutations. Only small fraction of acute myeloid leukemia (AML) cells carry BRCA mutations, hence the antitumor efficacy of PARP inhibitors (PARPi) against this malignancy is predicted to be limited; however, recent preclinical studies have demonstrated that PARPi monotherapy has modest efficacy in AML, while in combination with cytotoxic chemotherapy it has remarkable synergistic antitumor effects. Immunotherapy has revolutionized therapeutics in cancer treatment, and PARPi creates an ideal microenvironment for combination therapy with immunomodulatory agents by promoting tumor mutation burden. In this review, we summarize the role of PARP proteins in DNA damage response (DDR) pathways, and discuss recent preclinical studies using synthetic lethal modalities to treat AML. We also review the immunomodulatory effects of PARPi in AML preclinical models and propose future directions for therapy in AML, including combined targeting of the DDR and tumor immune microenvironment; such combination regimens will likely benefit patients with AML undergoing PARPi-mediated cancer therapy.Copyright © 2024 Bian, Liu, Yang and Sun.