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聚(ADP-核糖)聚合酶抑制剂在三阴性乳腺癌中的新型临床潜力:机制洞察与临床应用(综述)

Novel clinical potential of poly (ADP‑ribose) polymerase inhibitors in triple‑negative breast cancer: Mechanistic insights and clinical applications (Review).

作者信息

Han Yu, Wei Lei

机构信息

School of Basic Medical Sciences, Wuhan University, Wuhan, Hubei 430000, P.R. China.

出版信息

Oncol Lett. 2025 Mar 4;29(5):215. doi: 10.3892/ol.2025.14961. eCollection 2025 May.

Abstract

Breast cancer is one of the most prevalent malignant tumors worldwide, and triple-negative breast cancer (TNBC) presents a major therapeutic challenge due to the lack of effective targeted treatment options. Poly (ADP-ribose) polymerase (PARP) plays a critical role in DNA damage repair, and its inhibitors have shown significant therapeutic efficacy in patients with TNBC exhibiting breast cancer susceptibility gene (BRCA) mutations. The present review aimed to analyze the molecular mechanisms of cell death induced by DNA damage related to PAR and PARP, thoroughly exploring the role of PARP in regulatory pathways. Additionally, it intended to highlight clinical trials and therapeutic outcomes of PARP inhibitors currently used in TNBC treatment. In particular, the current review delves into the mechanisms of drug resistance, such as BRCA mutation reversion and PARP protein trapping, and examines potential strategies to overcome PARP inhibitor resistance in the future. Ultimately, the present study aims to offer novel perspectives and research directions for further optimizing the application of PARP inhibitors in TNBC therapy.

摘要

乳腺癌是全球最常见的恶性肿瘤之一,三阴性乳腺癌(TNBC)由于缺乏有效的靶向治疗选择而面临重大治疗挑战。聚(ADP - 核糖)聚合酶(PARP)在DNA损伤修复中起关键作用,其抑制剂已在携带乳腺癌易感基因(BRCA)突变的TNBC患者中显示出显著的治疗效果。本综述旨在分析与PAR和PARP相关的DNA损伤诱导细胞死亡的分子机制,深入探讨PARP在调控途径中的作用。此外,本综述旨在突出目前用于TNBC治疗的PARP抑制剂的临床试验和治疗结果。特别是,本综述深入研究了耐药机制,如BRCA突变逆转和PARP蛋白捕获,并探讨了未来克服PARP抑制剂耐药性的潜在策略。最终,本研究旨在为进一步优化PARP抑制剂在TNBC治疗中的应用提供新的视角和研究方向。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/17fe/11907691/e0ff56d94081/ol-29-05-14961-g00.jpg

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