The DOI matches its Crossref record; 56 of the 56 references it cites were found in a registry or an index.
PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer
Open accessAbstract
Pharmacologic inhibition of PARP is the primary therapeutic strategy for BRCA mutant ovarian cancer. However, most of patients carry wild-type BRCA1/2 with no significant clinical benefits from PARP inhibitors, calling for the needs to further understanding and developing new strategy when employing PARP inhibitors to treat ovarian cancer. Here, we show that ferroptosis, a form of regulated cell death driven by iron-dependent phospholipid peroxidation, is partly responsible for the efficacy of PARP inhibitor olaparib. Mechanistically, pharmacological inhibition or genetic deletion of PARP downregulates the expression of cystine transporter SLC7A11 in a p53-dependent manner. Consequently, decreased glutathione biosynthesis caused by SLC7A11 repression promotes lipid peroxidation and ferroptosis. Furthermore, ferroptosis perturbation results in significant resistance to olaparib without affecting DNA damage response, while boosting ferroptosis by ferroptosis inducers (FINs) synergistically sensitizes BRCA-proficient ovarian cancer cells and xenografts to PARP inhibitor. Together, our results reveal a previously unappreciated mechanism coupling ferroptosis to PARP inhibition and suggest the combination of PARP inhibitor and FINs in the treatment of BRCA-proficient ovarian cancer.
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Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
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Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
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The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
Bersuker, K., Hendricks, J. M., Li, Z., Magtanong, L., Ford, B., Tang, P. H., Roberts, M. A., Tong, B., Maimone, T. J., Zoncu, R., et al. (2019) · Nature · doi:10.1038/s41586-019-1705-2 · Cited by 3,703
Ovarian cancer statistics, 2018
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Ferroptosis as a p53-mediated activity during tumour suppression
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FSP1 is a glutathione-independent ferroptosis suppressor
Doll, S., Freitas, F. P., Shah, R., Aldrovandi, M., da Silva, M. C., Ingold, I., Goya Grocin, A., Xavier da Silva, T. N., Panzilius, E., Scheel, C. H., et al. (2019) · Nature · doi:10.1038/s41586-019-1707-0 · Cited by 3,341
PARP inhibitors: Synthetic lethality in the clinic
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CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
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Cited by
p53 in ferroptosis regulation: The new weapon for the old guardian
Liu, Y., & Gu, W. (2022) · Cell Death & Differentiation · doi:10.1038/s41418-022-00943-y · Cited by 540
The Role of Iron in Cancer Progression
Guo, Q., Li, L., Hou, S., Yuan, Z., Li, C., Zhang, W., Zheng, L., & Li, X. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.778492 · Cited by 150
Cheng, X., Zhao, F., Ke, B., Chen, D., & Liu, F. (2023) · Cancers · doi:10.3390/cancers15215209 · Cited by 44
Wu, M., Zhang, Z., Li, D., Ruan, X., Yang, J., Chen, S., Li, X., & Ling, W. (2025) · Theranostics · doi:10.7150/thno.102977 · Cited by 21
Metadata
- Authors
- Hong, T., Lei, G., Chen, X., Li, H., Zhang, X., Wu, N., Zhao, Y., Zhang, Y., & Wang, J.
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2021-06
- Volume
- 42
- Pages
- 101928
- ISSN
- 2213-2317 (ISSN-L)
- OpenAlex
- W3134087839
- Cited by
- 373
- References
- 56
- FWCI
- 36.17
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hong, T., Lei, G., Chen, X., Li, H., Zhang, X., Wu, N., Zhao, Y., Zhang, Y., & Wang, J. (2021). PARP inhibition promotes ferroptosis via repressing SLC7A11 and synergizes with ferroptosis inducers in BRCA-proficient ovarian cancer. Redox Biology. https://doi.org/10.1016/j.redox.2021.101928
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