Strategies for the prevention or reversal of PARP inhibitor resistance.

IF 2.9 3区 医学 Q2 ONCOLOGY Expert Review of Anticancer Therapy Pub Date : 2024-10-01 Epub Date: 2024-08-20 DOI:10.1080/14737140.2024.2393251
Zahi Mitri, Shaun M Goodyear, Gordon Mills
{"title":"Strategies for the prevention or reversal of PARP inhibitor resistance.","authors":"Zahi Mitri, Shaun M Goodyear, Gordon Mills","doi":"10.1080/14737140.2024.2393251","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Advances in our understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging the underlying tumor genomic instability and tumor-specific defects in DDR, Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.</p><p><strong>Areas covered: </strong>This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.</p><p><strong>Expert opinion: </strong>PARPi have proven to be a safe and effective therapy and represents a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.</p>","PeriodicalId":12099,"journal":{"name":"Expert Review of Anticancer Therapy","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Anticancer Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/14737140.2024.2393251","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/20 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Advances in our understanding of tumor biology shed light on hallmarks of cancer development and progression that include dysregulated DNA damage repair (DDR) machinery. Leveraging the underlying tumor genomic instability and tumor-specific defects in DDR, Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induced DNA damage emerges as a novel non-chemotherapy therapeutic opportunity. PARPis are currently approved in multiple tumor types, with the largest benefit seen in tumors with homologous recombination repair (HRR) deficiency, including germline and somatic mutations in BRCA1/2 genes (BRCA) and other pathway members such as PALB2 and Rad51c.

Areas covered: This review article summarizes the current approval landscape and known and proposed mechanisms of resistance to PARPi. Further, therapeutic strategies to overcome PARPi resistance are discussed, including ongoing clinical trials.

Expert opinion: PARPi have proven to be a safe and effective therapy and represents a cornerstone treatment across multiple solid tumor types. Elucidating innate and acquired mechanisms of resistance, coupled with the emergence of novel therapeutic options to capitalize on the activity of PARPi and prevent or reverse the acquisition of resistance, provides an opportunity to further expand the role of PARPi in cancer therapy.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
预防或逆转 PARP 抑制剂耐药性的策略。
导言:随着对肿瘤生物学认识的不断深入,人们发现了癌症发生和发展的特征,其中包括 DNA 损伤修复(DDR)机制失调。利用潜在的肿瘤基因组不稳定性和肿瘤特异性 DDR 缺陷,聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)诱导的 DNA 损伤成为一种新的非化疗治疗机会。PARPi目前已被批准用于多种肿瘤类型,其中同源重组修复(HRR)缺陷的肿瘤获益最大,包括BRCA1/2基因(BRCA)和其他通路成员(如PALB2和Rad51c)的种系突变和体细胞突变:这篇综述文章概述了目前的批准情况以及已知和提出的 PARPi 耐药机制。此外,文章还讨论了克服PARPi耐药性的治疗策略,包括正在进行的临床试验:PARPi已被证明是一种安全有效的疗法,是多种实体瘤类型治疗的基石。阐明先天和后天的耐药性机制,加上利用 PARPi 的活性、预防或逆转耐药性的新型治疗方案的出现,为进一步扩大 PARPi 在癌症治疗中的作用提供了机会。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
5.10
自引率
3.00%
发文量
100
审稿时长
4-8 weeks
期刊介绍: Expert Review of Anticancer Therapy (ISSN 1473-7140) provides expert appraisal and commentary on the major trends in cancer care and highlights the performance of new therapeutic and diagnostic approaches. Coverage includes tumor management, novel medicines, anticancer agents and chemotherapy, biological therapy, cancer vaccines, therapeutic indications, biomarkers and diagnostics, and treatment guidelines. All articles are subject to rigorous peer-review, and the journal makes an essential contribution to decision-making in cancer care. Comprehensive coverage in each review is complemented by the unique Expert Review format and includes the following sections: Expert Opinion - a personal view of the data presented in the article, a discussion on the developments that are likely to be important in the future, and the avenues of research likely to become exciting as further studies yield more detailed results Article Highlights – an executive summary of the author’s most critical points.
期刊最新文献
Statin use and ovarian cancer outcomes. Development of a nomogram for predicting postoperative recurrence of cervical intraepithelial neoplasia using immunohistochemical and clinical parameters. Impact of the 21-gene recurrence score testing on chemotherapy selection and clinical outcomes in T3N0 luminal breast cancer. The efficacy of trastuzumab-deruxtecan for the treatment of patients with advanced HER2-low breast cancer. Clinicopathological and prognostic significance of TIMP1 expression in gastric cancer: a systematic review and meta-analysis.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1