PARP抑制剂(PARPi)与免疫检查点抑制剂(ICIs)联合应用的研究进展。

IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS
Qi Liu, Chunmei Zhang, Yixuan Gao, Dongmei Feng, Duo Deng, Yun Pan
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引用次数: 0

摘要

DNA损伤修复(DDR)缺陷,如聚(adp -核糖)聚合酶(PARP)缺陷,通过促进DNA突变导致癌症发展,同时也暴露了癌症的特异性和易感性,从而提供了一种治疗选择。PARP抑制剂(PARPi)在治疗携带同源重组(HR)缺陷的肿瘤(如种系BRCA1/2突变)方面显示出巨大的前景。PARPi导致肿瘤新抗原、干扰素(IFN)和程序性细胞死亡1/程序性死亡配体1 (PD-1/PD-L1)的表达增加,并调节肿瘤微环境(TME),促进更深层次的抗肿瘤免疫治疗。靶向PD-1/PD-L1和细胞毒性t淋巴细胞相关蛋白4 (CTLA-4)的ICIs在治疗恶性肿瘤方面取得了令人印象深刻的成功。考虑到PARPi确实能增强ICI的抗肿瘤反应,PARPi与ICI的联合治疗逐渐成为ICI单药治疗效果不明显的个体的替代治疗选择。本文将重点介绍PARPi的发病机制和免疫应答,阐述其原理,并对其联合治疗的临床研究进行综述。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Research Progress on the Combination of PARP Inhibitors (PARPi) and Immune Checkpoint Inhibitors (ICIs)

Deficiencies in DNA damage repair (DDR), such as poly (ADP-ribose) polymerase (PARP) deficient, cause cancer development by promoting DNA mutations while also exposing the specificity and vulnerability of cancer to afford a treatment option. PARP inhibitor (PARPi) has shown great prospects in the treatment of tumors carrying homologous recombination (HR) deficiencies, such as germline BRCA1/2 mutations. PARPi leads to an increase in the expression of tumor neoantigen, interferon (IFN), and programmed cell death 1/programmed death-ligand 1 (PD-1/PD-L1), which also regulate the tumor microenvironment (TME), promoting a deeper anti-tumor immunotherapy. ICIs targeting PD-1/PD-L1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have achieved impressive success in the treatment of malignancies. Considering PARPi do enhance the anti-tumor response of ICIs, the combination of PARPi and ICIs has gradually become an alternative treatment option for individuals not receiving apparent efficacy from ICI monotherapy. In this review, the emphasis will be on the mechanisms and immune responses associated with PARPi, profess the principle, then count the clinical studies of this combination therapy.

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来源期刊
Advanced biology
Advanced biology Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
6.60
自引率
0.00%
发文量
130
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