PARP 抑制剂在卵巢癌中的临床应用:从分子机制到现状。

Clinical application of PARP inhibitors in ovarian cancer: from molecular mechanisms to the current status.

机构信息

Department of Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai200092, China.

Obstetrics and Gynecology, School of Medicine, Renji Hospital, Shanghai Jiaotong University, Shanghai, China.

出版信息

J Ovarian Res. 2023 Jan 7;16(1):6. doi: 10.1186/s13048-023-01094-5.

Abstract

As a kind of gynecological tumor, ovarian cancer is not as common as cervical cancer and breast cancer, but its malignant degree is higher. Despite the increasingly mature treatment of ovarian cancer, the five-year survival rate of patients is still less than 50%. Based on the concept of synthetic lethality, poly (ADP- ribose) polymerase (PARP) inhibitors target tumor cells with defects in homologous recombination repair(HRR), the most significant being the target gene Breast cancer susceptibility genes(BRCA). PARP inhibitors capture PARP-1 protein at the site of DNA damage to destroy the original reaction, causing the accumulation of PARP-DNA nucleoprotein complexes, resulting in DNA double-strand breaks(DSBs) and cell death. PARP inhibitors have been approved for the treatment of ovarian cancer for several years and achieved good results. However, with the widespread use of PARP inhibitors, more and more attention has been paid to drug resistance and side effects. Therefore, further research is needed to understand the mechanism of PARP inhibitors, to be familiar with the adverse reactions of the drug, to explore the markers of its efficacy and prognosis, and to deal with its drug resistance. This review elaborates the use of PARP inhibitors in ovarian cancer.

摘要

作为一种妇科肿瘤,卵巢癌不像宫颈癌和乳腺癌那么常见,但恶性程度更高。尽管卵巢癌的治疗越来越成熟,但患者的五年生存率仍低于 50%。基于合成致死的概念,聚(ADP-核糖)聚合酶(PARP)抑制剂针对同源重组修复(HRR)有缺陷的肿瘤细胞,其中最显著的是乳腺癌易感基因(BRCA)的靶基因。PARP 抑制剂在 DNA 损伤部位捕获 PARP-1 蛋白,破坏原反应,导致 PARP-DNA 核蛋白复合物的积累,导致 DNA 双链断裂(DSBs)和细胞死亡。PARP 抑制剂已被批准用于治疗卵巢癌数年,并取得了良好的效果。然而,随着 PARP 抑制剂的广泛应用,对其耐药性和副作用的关注越来越多。因此,需要进一步研究以了解 PARP 抑制剂的作用机制,熟悉药物的不良反应,探索其疗效和预后的标志物,并应对其耐药性。本文详细阐述了 PARP 抑制剂在卵巢癌中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f66/9826575/75d3625ab9fe/13048_2023_1094_Fig1_HTML.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索