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聚(二磷酸腺苷核糖)聚合酶抑制剂作用的泛肿瘤综述

A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors.

作者信息

Hage Chehade Chadi, Gebrael Georges, Sayegh Nicolas, Ozay Zeynep Irem, Narang Arshit, Crispino Tony, Golan Talia, Litton Jennifer K, Swami Umang, Moore Kathleen N, Agarwal Neeraj

机构信息

Division of Medical Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

出版信息

CA Cancer J Clin. 2025 Mar-Apr;75(2):141-167. doi: 10.3322/caac.21870. Epub 2025 Jan 10.

Abstract

Poly(adenosine diphosphate ribose) polymerase (PARP) inhibitors, such as olaparib, talazoparib, rucaparib, and niraparib, comprise a therapeutic class that targets PARP proteins involved in DNA repair. Cancer cells with homologous recombination repair defects, particularly BRCA alterations, display enhanced sensitivity to these agents because of synthetic lethality induced by PARP inhibitors. These agents have significantly improved survival outcomes across various malignancies, initially gaining regulatory approval in ovarian cancer and subsequently in breast, pancreatic, and prostate cancers in different indications. This review offers a comprehensive clinical overview of PARP inhibitor approvals, emphasizing their efficacy across different cancers based on landmark phase 3 clinical trials.

摘要

聚(腺苷二磷酸核糖)聚合酶(PARP)抑制剂,如奥拉帕利、他拉唑帕利、卢卡帕利和尼拉帕利,是一类靶向参与DNA修复的PARP蛋白的治疗药物。具有同源重组修复缺陷的癌细胞,尤其是BRCA改变的癌细胞,由于PARP抑制剂诱导的合成致死性,对这些药物表现出更高的敏感性。这些药物显著改善了各种恶性肿瘤的生存结果,最初在卵巢癌中获得监管批准,随后在不同适应症的乳腺癌、胰腺癌和前列腺癌中获批。本综述全面概述了PARP抑制剂的获批情况,基于具有里程碑意义的3期临床试验,强调了它们在不同癌症中的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebe0/11929130/bc68dc6f984a/CAAC-75-141-g002.jpg

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