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拓展PARP1及其抑制剂在癌症治疗中的视角:从DNA损伤修复到免疫调节

Expanding the Perspective on PARP1 and Its Inhibitors in Cancer Therapy: From DNA Damage Repair to Immunomodulation.

作者信息

Böhi Flurina, Hottiger Michael O

机构信息

Department of Molecular Mechanisms of Disease, University of Zurich, 8057 Zurich, Switzerland.

Cancer Biology Ph.D. Program, Life Science Zurich Graduate School, University of Zurich, 8057 Zurich, Switzerland.

出版信息

Biomedicines. 2024 Jul 20;12(7):1617. doi: 10.3390/biomedicines12071617.

Abstract

The emergence of PARP inhibitors as a therapeutic strategy for tumors with high genomic instability, particularly those harboring BRCA mutations, has advanced cancer treatment. However, recent advances have illuminated a multifaceted role of PARP1 beyond its canonical function in DNA damage repair. This review explores the expanding roles of PARP1, highlighting its crucial interplay with the immune system during tumorigenesis. We discuss PARP1's immunomodulatory effects in macrophages and T cells, with a particular focus on cytokine expression. Understanding these immunomodulatory roles of PARP1 not only holds promise for enhancing the efficacy of PARP inhibitors in cancer therapy but also paves the way for novel treatment regimens targeting immune-mediated inflammatory diseases.

摘要

聚(ADP - 核糖)聚合酶(PARP)抑制剂作为治疗基因组高度不稳定肿瘤,特别是那些携带BRCA突变肿瘤的一种治疗策略的出现,推动了癌症治疗的发展。然而,最近的进展揭示了PARP1除了在DNA损伤修复中的经典功能外,还具有多方面的作用。本综述探讨了PARP1不断扩展的作用,强调了其在肿瘤发生过程中与免疫系统的关键相互作用。我们讨论了PARP1在巨噬细胞和T细胞中的免疫调节作用,特别关注细胞因子的表达。了解PARP1的这些免疫调节作用不仅有望提高PARP抑制剂在癌症治疗中的疗效,也为针对免疫介导的炎症性疾病的新治疗方案铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbb9/11275100/48adcc0a4aaf/biomedicines-12-01617-g001.jpg

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