ArticleNature communications2024
Inhibition of GPX4 enhances CDK4/6 inhibitor and endocrine therapy activity in breast cancer.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- eGFP tagged ZnO nanoparticles from glioblastoma targeting ferroptosis and MRP1 in head and neck squamous cell carcinoma.Discover nano · 2026Article
- Molecular modulators of cyclin-dependent kinase 4/6 inhibitor response in experimental glioma identified through genome-wide CRISPR-Cas9 screening.Neuro-oncology · 2026Article
- Low-dose EGFR inhibition unlocks ferroptosis susceptibility to sensitize chemotherapy in EGFR-high triple-negative breast cancer.The Journal of biological chemistry · 2026Article
- The evolving landscape of CDK inhibitor use in breast cancer therapy and beyond.Nature reviews. Drug discovery · 2026Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- Programmed cell death and metastatic evolution in breast cancer: the role of anoikis, necroptosis, and ferroptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Cyclin-Dependent Kinases 4 and 6 Inhibitors: An Emerging Therapeutic Framework from Growth Suppression to Tumor Clearance.ACS pharmacology & translational science · 2026Review
- Cell size modulates ferroptosis susceptibility.eLife · 2026Article
- The role of estrogen and its receptors in the regulation of ferroptosis and autophagy.Molecular biology reports · 2026Review
- Metabolic Response to CDK4/6 Inhibition in ER+ Breast Cancer Creates a Therapeutic Vulnerability in Drug-Tolerant Persister Cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The Mechanism of G Protein-Coupled Receptor Regulation of Ferroptosis in Hepatic Ischemia-Reperfusion Injury.International journal of molecular sciences · 2026Review
- Phase separation of DDHD2 remodels lipid metabolism to dictate treatment sensitivity in luminal breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cell size modulates ferroptosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- Lipid Metabolism and Ferroptosis Resistance in Dormant Breast Cancer Cells: Emerging Therapeutic Vulnerabilities.Diagnostics (Basel, Switzerland) · 2026Review
- Dynamic Metabolic States in TNBC: Orchestrating Spatiotemporal Adaptation and Therapy.Oncology research · 2026Review
- Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.Frontiers in immunology · 2026Review
- Co-targeting ferroptosis and immune evasion through small molecules in breast cancer.Journal of translational internal medicine · 2025Article
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- The dual impact of oxidative stress on breast cancer.Scientific reports · 2025Article
- Adaptive multi-omics integration framework for breast cancer survival analysis.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
27 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CDK4/6 inhibition in combination with endocrine therapy is the standard of care for estrogen receptor (ER+) breast cancer, and although cytostasis is frequently observed, new treatment strategies that enhance efficacy are required. Here, we perform two independent genome-wide CRISPR screens to identify genetic determinants of CDK4/6 and endocrine therapy sensitivity. Genes involved in oxidative stress and ferroptosis modulate sensitivity, with GPX4 as the top sensitiser in both screens. Depletion or inhibition of GPX4 increases sensitivity to palbociclib and giredestrant, and their combination, in ER+ breast cancer models, with GPX4 null xenografts being highly sensitive to palbociclib. GPX4 perturbation additionally sensitises triple negative breast cancer (TNBC) models to palbociclib. Palbociclib and giredestrant induced oxidative stress and disordered lipid metabolism, leading to a ferroptosis-sensitive state. Lipid peroxidation is promoted by a peroxisome AGPAT3-dependent pathway in ER+ breast cancer models, rather than the classical ACSL4 pathway. Our data demonstrate that CDK4/6 and ER inhibition creates vulnerability to ferroptosis induction, that could be exploited through combination with GPX4 inhibitors, to enhance sensitivity to the current therapies in breast cancer.
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