Therapeutic advances and application of PARP inhibitors in breast cancer

Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cel...

Full description

Saved in:
Bibliographic Details
Main Authors: Teng Zhou, Jian Zhang
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S193652332500141X
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849730322319540224
author Teng Zhou
Jian Zhang
author_facet Teng Zhou
Jian Zhang
author_sort Teng Zhou
collection DOAJ
description Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.
format Article
id doaj-art-615896d5f47d45a4a828edc06e07c277
institution DOAJ
issn 1936-5233
language English
publishDate 2025-07-01
publisher Elsevier
record_format Article
series Translational Oncology
spelling doaj-art-615896d5f47d45a4a828edc06e07c2772025-08-20T03:08:55ZengElsevierTranslational Oncology1936-52332025-07-015710241010.1016/j.tranon.2025.102410Therapeutic advances and application of PARP inhibitors in breast cancerTeng Zhou0Jian Zhang1Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR ChinaDepartment of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, PR China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, PR China; Corresponding author at: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, PR China.Targeting of DNA repair pathway is the main therapeutic approach for BRCA1 and BRCA2 associated tumors, including breast cancer. BRCA1/2 genes play a pivotal role in HRR pathway. Mutations in BRCA1/2 leads to DDR deficiency, which cause the increasing of genome instability, thus rendering cancer cells vulnerable to inhibition of DNA repair related proteins, such as PARP1. Pre-clinical studies has demonstrated that cancer cells with BRCA1/2 deficient are sensitive to PARPi, which are an emerging class of small molecule drug. Several clinical trials demonstrated the promising efficacy of PARP inhibitors for BRCA1/2 mutated breast cancer patient through selectively induce synthetic lethality cancer cells. Currently, four PARP inhibitors had been approved by FDA for clinical use. PARPi demonstrated to improve progression-free survival, while resistance to PARPi is inevitable. In this review article, we highlighted the advances in the PARPi clinical trials, resistance mechanism and coping strategies in breast cancer patients. We also summarized the international guideline and recommendations on PARP inhibitor usage in breast cancer.http://www.sciencedirect.com/science/article/pii/S193652332500141XBreast cancerBRCA1/2 mutationsPoly (ADP-ribose) polymerasePARPiOlaparib
spellingShingle Teng Zhou
Jian Zhang
Therapeutic advances and application of PARP inhibitors in breast cancer
Translational Oncology
Breast cancer
BRCA1/2 mutations
Poly (ADP-ribose) polymerase
PARPi
Olaparib
title Therapeutic advances and application of PARP inhibitors in breast cancer
title_full Therapeutic advances and application of PARP inhibitors in breast cancer
title_fullStr Therapeutic advances and application of PARP inhibitors in breast cancer
title_full_unstemmed Therapeutic advances and application of PARP inhibitors in breast cancer
title_short Therapeutic advances and application of PARP inhibitors in breast cancer
title_sort therapeutic advances and application of parp inhibitors in breast cancer
topic Breast cancer
BRCA1/2 mutations
Poly (ADP-ribose) polymerase
PARPi
Olaparib
url http://www.sciencedirect.com/science/article/pii/S193652332500141X
work_keys_str_mv AT tengzhou therapeuticadvancesandapplicationofparpinhibitorsinbreastcancer
AT jianzhang therapeuticadvancesandapplicationofparpinhibitorsinbreastcancer