PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials.

IF 4.7 2区 医学 Q1 ONCOLOGY
Current Oncology Reports Pub Date : 2025-05-01 Epub Date: 2025-04-07 DOI:10.1007/s11912-025-01669-z
Minatoullah Habaka, Gordon R Daly, Deborah Shinyanbola, Mohammad Alabdulrahman, Jason McGrath, Gavin P Dowling, Cian Hehir, Helen Ye Rim Huang, Arnold D K Hill, Damir Varešlija, Leonie S Young
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引用次数: 0

Abstract

Purposeof review: Poly (ADP-ribose) polymerases (PARPs) are enzymes essential for detecting and repairing DNA damage through poly-ADP-ribosylation. In cancer, cells with deficiencies in homologous recombination repair mechanisms often become more dependent on PARP-mediated repair mechanisms to effectively repair dsDNA breaks. As such, PARP inhibitors (PARPis) were introduced into clinical practice, serving as a key targeted therapy option through synthetic lethality in the treatment of cancers with homologous recombination repair deficiency (HRD). Though PARPis are currently approved in the adjuvant setting for several cancer types such as ovarian, breast, prostate and pancreatic cancer, their potential role in the neoadjuvant setting remains under investigation. This review outlines the rationale for using PARPi in the neoadjuvant setting and evaluates findings from early and ongoing clinical trials.

Recent findings: Our analysis indicates that numerous studies have explored PARPi as a neoadjuvant treatment for HRD-related cancers. The majority of neoadjuvant PARPi trials have been performed in breast and ovarian cancer, while phase II/III evidence supporting efficacy in prostate and pancreatic cancers remains limited. Studies are investigating PARPi in the neoadjuvant setting of HRD-related cancers. Future research should prioritize combination strategies with immune checkpoint inhibitors and expand outcome measures to include patient satisfaction and quality-of-life metrics.

PARP抑制剂在新辅助治疗中的应用全面概述其使用的基本原理,过去和正在进行的临床试验。
综述目的:聚adp核糖聚合酶(PARPs)是通过聚adp核糖基化检测和修复DNA损伤所必需的酶。在癌症中,缺乏同源重组修复机制的细胞往往更依赖parp介导的修复机制来有效修复dsDNA断裂。因此,PARP抑制剂(PARPis)被引入临床实践,作为一种关键的靶向治疗选择,通过合成致死性治疗同源重组修复缺陷(HRD)的癌症。尽管PARPis目前已被批准用于卵巢癌、乳腺癌、前列腺癌和胰腺癌等几种癌症的辅助治疗,但其在新辅助治疗中的潜在作用仍在研究中。这篇综述概述了在新辅助治疗中使用PARPi的基本原理,并评估了早期和正在进行的临床试验的结果。最近的发现:我们的分析表明,许多研究已经探索了PARPi作为hrd相关癌症的新辅助治疗。大多数新辅助PARPi试验已在乳腺癌和卵巢癌中进行,而支持前列腺癌和胰腺癌疗效的II/III期证据仍然有限。研究正在调查PARPi在hrd相关癌症的新辅助治疗中的作用。未来的研究应优先考虑与免疫检查点抑制剂的联合策略,并扩大结果测量,包括患者满意度和生活质量指标。
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
CiteScore
8.50
自引率
0.00%
发文量
187
审稿时长
6-12 weeks
期刊介绍: This journal aims to review the most important, recently published clinical findings in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to serve all those involved in the care of those affected by cancer. We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as cancer prevention, leukemia, melanoma, neuro-oncology, and palliative medicine. 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.
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