The DOI matches its Crossref record; 71 of the 71 references it cites were found in a registry or an index.
Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy
Open accessAbstract
Treatment of triple-negative breast cancer (TNBC) remains challenging. Deciphering the orchestration of metabolic pathways in regulating ferroptosis will provide new insights into TNBC therapeutic strategies. Here, we integrated the multiomics data of our large TNBC cohort (n = 465) to develop the ferroptosis atlas. We discovered that TNBCs had heterogeneous phenotypes in ferroptosis-related metabolites and metabolic pathways. The luminal androgen receptor (LAR) subtype of TNBC was characterized by the upregulation of oxidized phosphatidylethanolamines and glutathione metabolism (especially GPX4), which allowed the utilization of GPX4 inhibitors to induce ferroptosis. Furthermore, we verified that GPX4 inhibition not only induced tumor ferroptosis but also enhanced antitumor immunity. The combination of GPX4 inhibitors and anti-PD1 possessed greater therapeutic efficacy than monotherapy. Clinically, higher GPX4 expression correlated with lower cytolytic scores and worse prognosis in immunotherapy cohorts. Collectively, this study demonstrated the ferroptosis landscape of TNBC and revealed an innovative immunotherapy combination strategy for refractory LAR tumors.
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Cites
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ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
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The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis
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Cited by
The role of lipid metabolic reprogramming in tumor microenvironment
Yang, K., Wang, X., Song, C., He, Z., Wang, R., Xu, Y., Jiang, G., Wan, Y., Mei, J., & Mao, W. (2023) · Theranostics · doi:10.7150/thno.82920 · Cited by 270
Wu, S., Wu, X., Wang, Q., Chen, Z., Li, L., Chen, H., & Qi, H. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.156130 · Cited by 27
Metadata
- Authors
- Yang, F., Xiao, Y., Ding, J.-H., Jin, X., Ma, D., Li, D.-Q., Shi, J.-X., Huang, W., Wang, Y.-P., Jiang, Y.-Z., & Shao, Z.-M.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2023-01
- Volume
- 35
- Issue
- 1
- Pages
- 84-100.e8
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W4306410243
- Cited by
- 624
- References
- 71
- FWCI
- 67.65
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Yang, F., Xiao, Y., Ding, J.-H., Jin, X., Ma, D., Li, D.-Q., Shi, J.-X., Huang, W., Wang, Y.-P., Jiang, Y.-Z., & Shao, Z.-M. (2023). Ferroptosis heterogeneity in triple-negative breast cancer reveals an innovative immunotherapy combination strategy. Cell Metabolism. https://doi.org/10.1016/j.cmet.2022.09.021
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