Targeting PARP1: A Promising Approach for Next-Generation Poly (ADP-ribose) Polymerase Inhibitors.

IF 1 Q4 ONCOLOGY

Current Breast Cancer Reports Pub Date : 2025-01-01 Epub Date: 2025-06-12 DOI:10.1007/s12609-025-00582-5

Alo Ray, Mateusz Opyrchal

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引用次数: 0

Abstract

Limitations of poly adp‒ribose polymerase parp inhibitors: PARPis have demonstrated efficacy in BRCA-mutated cancers deficient in homologous recombination repair. Furthermore, PARPis have shown efficacy in BRCA-wild-type cancers with a homologous recombination deficiency phenotype known as BRCAness. Current clinically approved PARPis inhibit both PARP1 and PARP2, and their clinical promise is limited by toxicity, resistance, and a lack of combination partners.

Recent findings: PARP2 inhibition is associated with hematological toxicity, affecting the tolerability and efficacy of monotherapy and combination therapies. Furthermore, synthetic lethality in BRCA-mutated cancers depends mostly on PARP1, whereas PARP2 is not essential. These findings promoted the development of next-generation PARPis with greater selectivity for PARP1 than for PARP2.

Summary: In this review, we discuss the next-generation PARPis that target PARP1 and show promise in terms of improved safety, tolerability, pharmacological profiles, and efficacy compared to existing clinically approved PARPis. These next-generation PARP1-selective inhibitors hold significant promises for improving the survival and outcomes of cancer patients.

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靶向PARP1：下一代聚（adp -核糖）聚合酶抑制剂的一种有希望的方法。

聚腺苷核糖聚合酶parp抑制剂的局限性：parp抑制剂已被证明对缺乏同源重组修复的brca突变癌症有效。此外，PARPis在具有同源重组缺陷表型（BRCAness）的brca野生型癌症中显示出疗效。目前临床批准的PARPis同时抑制PARP1和PARP2，其临床前景受到毒性、耐药性和缺乏联合伙伴的限制。最近发现：PARP2抑制与血液毒性相关，影响单药和联合治疗的耐受性和疗效。此外，brca突变癌症的合成致死率主要取决于PARP1，而PARP2不是必需的。这些发现促进了下一代parpi的发展，PARP1比PARP2具有更大的选择性。摘要：在这篇综述中，我们讨论了针对PARP1的下一代PARPis，与现有临床批准的PARPis相比，它们在安全性、耐受性、药理学特征和疗效方面都有改善。这些新一代parp1选择性抑制剂有望改善癌症患者的生存和预后。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current Breast Cancer Reports ONCOLOGY-

CiteScore

1.60

自引率

0.00%

发文量

期刊介绍： This journal aims to review the most important, recently published clinical findings related to the diagnosis, treatment, management, and prevention of breast cancer. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those with the disease. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as prevention, systemic therapy, and translational research. Section Editors, in turn, select topics for which leading experts contribute comprehensive review articles that emphasize new developments and recently published papers of major importance, highlighted by annotated reference lists. An international Editorial Board reviews the annual table of contents, suggests articles of special interest to their country/region, and ensures that topics are current and include emerging research. Commentaries from well-known figures in the field are also provided.