Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies

Muhammad SHOAIB; Zeeshan Ahmad BHUTTA; Ahsan JAVED; Muhammad Nabeel AMJAD; Wenzhu LI; Kyung-Chul CHOI; Wanxia PU

doi:10.1631/jzus.B2400146

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Review | Updated：2026-01-27

Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies
Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies
PARP抑制剂在癌症治疗中的未来：通过联合疗法克服耐药性并提高疗效
Journal of Zhejiang University-SCIENCE B Vol. 27, Issue 1, Pages: 23-43(2026)
Affiliations：

1.Key Laboratory of New Animal Drug Project, Gansu Province / Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture and Rural Affairs / Lanzhou Institute of Husbandry and Pharmaceutical Sciences of the Chinese Academy of Agricultural Sciences, Lanzhou 730050, China
2.Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Republic of Korea
3.Basic Health Unit Haft Maddar, Tehsil and District Nankana Sahib, Punjab 37000, Pakistan
4.CAS Key Laboratory of Molecular Virology and Immunology, Shanghai Institute of Immunity and Infection, Chinese Academy of Sciences, Shanghai 200031, China
5.University of Chinese Academy of Sciences, Beijing 100049, China
6.Department of Clinical Medicine, Qilihe District People’s Hospital of Lanzhou, Lanzhou 730050, China
Funds：
DOI：10.1631/jzus.B2400146
CLC：
CSTR：
Received：13 March 2024，

Revised：2024-08-28，

Published Online：11 December 2025，

Published：27 January 2026
Accepted：

Muhammad SHOAIB,Zeeshan Ahmad BHUTTA,Ahsan JAVED等.PARP抑制剂在癌症治疗中的未来：通过联合疗法克服耐药性并提高疗效[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(01):23-43.

Muhammad SHOAIB, Zeeshan Ahmad BHUTTA, Ahsan JAVED, et al. Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(1): 23-43.
Muhammad SHOAIB,Zeeshan Ahmad BHUTTA,Ahsan JAVED等.PARP抑制剂在癌症治疗中的未来：通过联合疗法克服耐药性并提高疗效[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2026,27(01):23-43. DOI： 10.1631/jzus.B2400146.

Muhammad SHOAIB, Zeeshan Ahmad BHUTTA, Ahsan JAVED, et al. Future of PARP inhibitors in cancer treatment: overcoming resistance and enhancing efficacy with combination therapies[J]. Journal of Zhejiang University-SCIENCE B, 2026, 27(1): 23-43. DOI： 10.1631/jzus.B2400146.

摘要

聚腺苷二磷酸核糖聚合酶（PARP）作为一个蛋白质家族，在不同细胞过程中起着至关重要的作用，包括DNA修复、细胞死亡和染色质结构变化。PARP抑制剂（PARPi）在抗癌治疗中的意义在于其特异性破坏DNA修复途径的能力，可导致癌细胞的靶向死亡，特别是在具有同源重组缺陷（HRD）的癌症中。这些抑制剂已被批准用于治疗包括卵巢癌、乳腺癌和胰腺癌在内的几种癌症。尽管PARPi具有良好的治疗前景，但其耐药性的产生却是一个巨大障碍，限制了其整体疗效。本综述对与PARPi抗性相关的潜在机制进行了全面描述，同时深入研究了克服耐药性的潜在策略，并评估了PARPi与替代疗法联合使用的治疗潜力。

Abstract

Poly(ADP-ribose) polymerase (PARP) is a family of proteins that play a crucial role in diverse cellular processes

including DNA repair

cell death

and changes in chromatin structure. PARP inhibitors (PARPi) have been recognized as notable agents in the realm of anticancer therapeutics owing to their capacity to specifically impact DNA repair pathways

thereby inducing targeted death of cancerous cells

particularly in cancers with homologous recombination deficiency (HRD). These inhibitors have been approved for the treatment of several cancers

such as ovarian

breast

and pancreatic cancers. Despite their promising therapeutic attributes

developing resistance to PARPi presents a formidable obstacle

curtailing their overall efficacy. This article presents a comprehensive description of the potential mechanisms related to PARPi resistance

an in-depth study of potential strategies to overcome resistance

and an assessment of the therapeutic potential of the PARPi in combination with alternative therapies.

关键词

Keywords

references

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