Poly(ADP-ribose) Polymerase Inhibitor Talazoparib Inhibits DNA Damage Repair in Breast Cancer Cell Lines With or Without BRCA1/2 Mutation
6 affiliations
- 1Cancer Research Institute, Seoul National University, Seoul, Korea .
- 2Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea .
- 3Department of Internal Medicine and Translational Medicine, Seoul National University College of Medicine, Seoul, Korea .
- 4Interdisciplinary Programs in Cancer Biology Major, Seoul National University Graduate School, Seoul, Korea .
- 5Department of Internal Medicine, University of California San Francisco, San Francisco, USA .
- 6Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea .
Abstract
Purpose: Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. Although PARP inhibitor sensitivity has traditionally been attributed to synthetic lethality in tumors with BRCA1/2 mutations or homologous recombination repair deficiency, emerging evidence indicates that clinical and preclinical activity may extend to selected tumors beyond those harboring germline BRCA1/2 mutations. This study investigated the mechanism underlying talazoparib efficacy in both BRCA1/2-mutant and BRCA1/2 wild-type breast cancer cells.
Methods: Twenty-one breast cancer cell lines, including both BRCA-1/2-mutant and wild-type cells, were treated with talazoparib, and the effects of the treatment on cell proliferation, cell cycle progression, DNA damage accumulation, and apoptosis were evaluated.
Results: Talazoparib demonstrated antiproliferative effects in BRCA1/2-mutant and wild-type cells in a long-term culture system, as assessed by colony formation assays. Accumulation of single-stranded and double-stranded DNA damage was observed in talazoparib-sensitive cell lines, as indicated by phosphorylated RPA and γ-H2AX, respectively. This was accompanied by G2/M arrest and subsequent apoptosis, as evidenced by cleaved caspase-3 expression and Annexin V staining. Abnormal mitotic nuclei were observed in talazoparib-sensitive cell lines, which also exhibited potent and sustained PARP1 trapping on chromatin.
Conclusion: Talazoparib exerts anti-tumor effects in BRCA1/2-mutant and wild-type breast cancer cells by promoting the formation of abnormal mitotic nuclei and inducing apoptosis in sensitive cells. Our findings support the potential therapeutic application of talazoparib beyond its current indications for BRCA1/2-mutant tumors.
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BibTeX
@article{lee2026polyadpribose,
title = {{Poly(ADP-ribose) Polymerase Inhibitor Talazoparib Inhibits DNA Damage Repair in Breast Cancer Cell Lines With or Without BRCA1/2 Mutation}},
author = {Miso Lee and Kyung-Hun Lee and Ahrum Min and Sujin Ham and Jihyeon Moon and Yu-Jin Kim and Hae Min Hwang and Youlim Noh and Eunice Yoojin Lee and Hye Yeon Park and Jiwon Koh and Changhee Park and Dae-Won Lee and Seock-Ah Im},
journal = {Journal of Breast Cancer},
year = {2026},
month = sep,
doi = {10.4048/jbc.2026.0085},
url = {https://doi.org/10.4048/jbc.2026.0085},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Poly(ADP-ribose) Polymerase Inhibitor Talazoparib Inhibits DNA Damage Repair in Breast Cancer Cell Lines With or Without BRCA1/2 Mutation
AU - Miso Lee
AU - Kyung-Hun Lee
AU - Ahrum Min
AU - Sujin Ham
AU - Jihyeon Moon
AU - Yu-Jin Kim
AU - Hae Min Hwang
AU - Youlim Noh
AU - Eunice Yoojin Lee
AU - Hye Yeon Park
AU - Jiwon Koh
AU - Changhee Park
AU - Dae-Won Lee
AU - Seock-Ah Im
PY - 2026
DA - 2026/09/10
JO - Journal of Breast Cancer
DO - 10.4048/jbc.2026.0085
UR - https://doi.org/10.4048/jbc.2026.0085
AB - Purpose: Talazoparib is a potent poly(ADP-ribose) polymerase (PARP) inhibitor approved for use in patients with germline BRCA1/2-mutated human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer. Although PARP inhibitor sensitivity has traditionally been attributed to synthetic lethality in tumors with BRCA1/2 mutations or homologous recombination repair deficiency, emerging evidence indicates that clinical and preclinical activity may extend to selected tumors beyond those harboring germline BRCA1/2 mutations. This study investigated the mechanism underlying talazoparib efficacy in both BRCA1/2-mutant and BRCA1/2 wild-type breast cancer cells. Methods: Twenty-one breast cancer cell lines, including both BRCA-1/2-mutant and wild-type cells, were treated with talazoparib, and the effects of the treatment on cell proliferation, cell cycle progression, DNA damage accumulation, and apoptosis were evaluated. Results: Talazoparib demonstrated antiproliferative effects in BRCA1/2-mutant and wild-type cells in a long-term culture system, as assessed by colony formation assays. Accumulation of single-stranded and double-stranded DNA damage was observed in talazoparib-sensitive cell lines, as indicated by phosphorylated RPA and γ-H2AX, respectively. This was accompanied by G2/M arrest and subsequent apoptosis, as evidenced by cleaved caspase-3 expression and Annexin V staining. Abnormal mitotic nuclei were observed in talazoparib-sensitive cell lines, which also exhibited potent and sustained PARP1 trapping on chromatin. Conclusion: Talazoparib exerts anti-tumor effects in BRCA1/2-mutant and wild-type breast cancer cells by promoting the formation of abnormal mitotic nuclei and inducing apoptosis in sensitive cells. Our findings support the potential therapeutic application of talazoparib beyond its current indications for BRCA1/2-mutant tumors.
SN - 1738-6756
SN - 2092-9900
ER -