{"title":"在卵巢癌中导航PARP抑制剂耐药性：将机制见解连接到临床转化。","authors":"Ziyi Wang, Yuting Liu, Qing Yang","doi":"10.1007/s11864-025-01347-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Opinion statement: </strong>PARP inhibitors (PARPi) are increasingly vital in treating, particularly in individuals exhibiting homologous recombination deficiency (HRD), harnessing synthetic lethality to target tumor cells. However, PARPi resistance severely restricts their sustained efficacy, posing a significant clinical obstacle requiring a detailed exploration of its mechanisms and solutions. This review elucidates the underlying mechanisms of PARPi resistance, assesses biomarker-driven predictive tools, and explores novel strategies to improve therapeutic outcomes. This review critically assesses biomarker-driven strategies for resistance prediction, such as genomic profiling, functional assays, dynamic circulating tumor DNA (ctDNA) monitoring, and emerging markers, to refine patient stratification. Moreover, this review systematically dissects PARPi resistance, including genomic alterations, homologous recombination (HR) restoration, replication fork stabilization, enhanced drug efflux, reduced PARP1 trapping, and microenvironmental influences. In addition, therapeutic tactics to prevent or overcome resistance are evaluated, encompassing sequential PARPi use, combinations with chemotherapy, immunotherapy, antiangiogenic agents, and DNA damage response (DDR) inhibitors, alongside innovative approaches like antibody-drug conjugates (ADCs). Bridging mechanistic and clinical perspectives, this review promotes a multidisciplinary approach to optimize PARPi-based treatments, addressing current challenges in ovarian cancer management.</p>","PeriodicalId":50600,"journal":{"name":"Current Treatment Options in Oncology","volume":" ","pages":"797-819"},"PeriodicalIF":4.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.\",\"authors\":\"Ziyi Wang, Yuting Liu, Qing Yang\",\"doi\":\"10.1007/s11864-025-01347-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Opinion statement: </strong>PARP inhibitors (PARPi) are increasingly vital in treating, particularly in individuals exhibiting homologous recombination deficiency (HRD), harnessing synthetic lethality to target tumor cells. However, PARPi resistance severely restricts their sustained efficacy, posing a significant clinical obstacle requiring a detailed exploration of its mechanisms and solutions. This review elucidates the underlying mechanisms of PARPi resistance, assesses biomarker-driven predictive tools, and explores novel strategies to improve therapeutic outcomes. This review critically assesses biomarker-driven strategies for resistance prediction, such as genomic profiling, functional assays, dynamic circulating tumor DNA (ctDNA) monitoring, and emerging markers, to refine patient stratification. Moreover, this review systematically dissects PARPi resistance, including genomic alterations, homologous recombination (HR) restoration, replication fork stabilization, enhanced drug efflux, reduced PARP1 trapping, and microenvironmental influences. In addition, therapeutic tactics to prevent or overcome resistance are evaluated, encompassing sequential PARPi use, combinations with chemotherapy, immunotherapy, antiangiogenic agents, and DNA damage response (DDR) inhibitors, alongside innovative approaches like antibody-drug conjugates (ADCs). Bridging mechanistic and clinical perspectives, this review promotes a multidisciplinary approach to optimize PARPi-based treatments, addressing current challenges in ovarian cancer management.</p>\",\"PeriodicalId\":50600,\"journal\":{\"name\":\"Current Treatment Options in Oncology\",\"volume\":\" \",\"pages\":\"797-819\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current Treatment Options in Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11864-025-01347-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Treatment Options in Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11864-025-01347-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Navigating PARP Inhibitor Resistance in Ovarian Cancer: Bridging Mechanistic Insights To Clinical Translation.
Opinion statement: PARP inhibitors (PARPi) are increasingly vital in treating, particularly in individuals exhibiting homologous recombination deficiency (HRD), harnessing synthetic lethality to target tumor cells. However, PARPi resistance severely restricts their sustained efficacy, posing a significant clinical obstacle requiring a detailed exploration of its mechanisms and solutions. This review elucidates the underlying mechanisms of PARPi resistance, assesses biomarker-driven predictive tools, and explores novel strategies to improve therapeutic outcomes. This review critically assesses biomarker-driven strategies for resistance prediction, such as genomic profiling, functional assays, dynamic circulating tumor DNA (ctDNA) monitoring, and emerging markers, to refine patient stratification. Moreover, this review systematically dissects PARPi resistance, including genomic alterations, homologous recombination (HR) restoration, replication fork stabilization, enhanced drug efflux, reduced PARP1 trapping, and microenvironmental influences. In addition, therapeutic tactics to prevent or overcome resistance are evaluated, encompassing sequential PARPi use, combinations with chemotherapy, immunotherapy, antiangiogenic agents, and DNA damage response (DDR) inhibitors, alongside innovative approaches like antibody-drug conjugates (ADCs). Bridging mechanistic and clinical perspectives, this review promotes a multidisciplinary approach to optimize PARPi-based treatments, addressing current challenges in ovarian cancer management.
期刊介绍：
This journal aims to review the most important, recently published treatment option advances in the field of oncology. By providing clear, insightful, balanced contributions by international experts, the journal intends to facilitate worldwide approaches to cancer treatment.
We accomplish this aim by appointing international authorities to serve as Section Editors in key subject areas, such as endocrine tumors, lymphomas, neuro-oncology, and cancers of the breast, head and neck, lung, skin, gastrointestinal tract, and genitourinary region. 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. We also provide commentaries from well-known oncologists, and 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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
