Update on Combination Strategies of PARP Inhibitors - Journal Article Review

Sep 21, 2026

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PARP inhibitors have transformed cancer treatment, especially for tumors with homologous recombination repair defects in HRR-related genes such as BRCA1 and BRCA2. Despite promising results, acquired drug resistance, severe side effects, and limited benefit for patients without homologous recombination deficiency remain major obstacles. Combination regimens have been developed to address these limitations, including immune checkpoint inhibitor combinations, antiangiogenic strategies, and small-molecule approaches. Yet efficacy and overlapping toxicity differ across studies, restricting broader use. This review explains PARP inhibitor mechanisms and limits, summarizes recent combination research across multiple drugs, and aims to provide a more comprehensive evidence base.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Key Points

Introduction

PARP Inhibitors

Mechanisms of PARPis-mediated Cytotoxicity

Update on Combination Strategies of PARP Inhibitors Cancer Control Volume 31: 1–15 © The Author(s) 2024 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions) [DOI: 10.1177/10732748241298329](DOI: 10.1177/10732748241298329)[ ](DOI: 10.1177/10732748241298329)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx) Zhuoqun Lin 1,*, Lingfang Wang, PhD2,*, Ziyu Xing 1,*, Fenfen Wang, MD2,3,4, and Xiaodong Cheng, MD2,3,4,5 􀀁 Abstract The application of PARP inhibitors has revolutionized cancer treatment and has achieved signiﬁcant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic beneﬁts for patients without homologous recombination deﬁciency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efﬁcacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efﬁciency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efﬁcacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic. Keywords PARP inhibitors, homologous repair, combination therapy, cancer treatment Received August 9, 2024. Received revised October 7, 2024. Accepted for publication October 21, 2024. 1 Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, China 2Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China 3Gynecological Oncology Department, Women’s Hospital, Zhejiang University School of Medicine, Hangzhou, P. R. China 4Zhejiang Provincial Clinical Research Center for Obstetrics and Gynecology, Hangzhou, P. R. China 5Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Hangzhou, P. R. China *These authors have contributed equally to this work and share the ﬁrst authorship. Corresponding Authors: Fenfen Wang, MD, Gynecological Oncology Department, Women’s Hospital, Zhejiang University School of Medicine, No. 1 Xueshi Road, Hangzhou, Zhejiang 310006, P. R. China. [Email:](Email: wangfenfen@zju.edu.cn)[ wangfenfen@zju.edu.cn](Email: wangfenfen@zju.edu.cn) Xiaodong Cheng, MD, Women’s Hospital School of Medicine Zhejiang University, 1 Xueshi Road, Shangcheng District, Hangzhou 310006, China. Email: [chengxd@zju.edu.cn](chengxd@zju.edu.cn) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as speciﬁed on the SAGE and Open Access pages ([https://us.sagepub.com/en-us/nam/open-access-at-sage](https://us.sagepub.com/en-us/nam/open-access-at-sage)). Data Availability Statement included at the end of the article Key Points 1. This comprehensive literature review presents an updated combination therapy of PARP i

FAQs

Why are PARP inhibitors especially effective in BRCA1/BRCA2-related cancers?

They exploit synthetic lethality between PARP-mediated single-strand breaks and homologous recombination repair, which is frequently impaired in tumors carrying BRCA1/2 mutations.

What main limitations of PARP inhibitors motivate combination strategies?

Key issues include acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency.

Which combination approaches are highlighted as well-studied in the review?

Combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are discussed, alongside emerging options such as HSP90 inhibitors, BET inhibitors, and novel delivery carriers.

Sep 21, 2026

Uploaded by Skyler