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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-07-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S193652332500141X |
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| 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 |