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
{"title":"PARP Inhibitors in the Neoadjuvant Setting; A Comprehensive Overview of the Rationale for their Use, Past and Ongoing Clinical Trials.","authors":"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","doi":"10.1007/s11912-025-01669-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purposeof review: </strong>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.</p><p><strong>Recent findings: </strong>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.</p>","PeriodicalId":10861,"journal":{"name":"Current Oncology Reports","volume":" ","pages":"533-551"},"PeriodicalIF":4.7000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081494/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Oncology Reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11912-025-01669-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/4/7 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
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.
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.