ReviewTranslational breast cancer research : a journal focusing on translational research in breast cancer2026
Biomarkers of primary and secondary resistance to cyclin dependent kinases 4 and 6 inhibitors in metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer: a narrative review.
Review in Translational breast cancer research : a journal focusing on translational research in breast cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- NUPR1 in breast cancer: mechanisms and potential applications.Frontiers in physiology · 2026Review
Corrections and comments
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Authors and funding
2 authors.
Funding
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Abstract
Background and Objective: Cyclin dependent kinases 4 and 6 (CDK4/6) inhibitors are a class of drugs that are used in the first-line therapy of metastatic estrogen receptor (ER) positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer and in the adjuvant therapy of the same cancers. Three drugs of the class, abemaciclib, palbociclib and ribociclib, are currently approved in partially overlapping indications. This review discusses biomarkers for prediction of efficacy of CDK4/6 inhibitors in breast cancer therapy and the potential for overcoming arising resistance. Methods: A literature search was performed using the PubMed/Medline database and the proceedings of relevant congresses. Search was concluded on March 31, 2025. Key Content and Findings: Combinations of CDK4/6 inhibitors with hormonal agents have improved survival outcomes of metastatic ER-positive/HER2-negative breast cancer patients, but resistance develops almost invariably. In addition, a minority of patients display primary resistance to the combinations. Significant efforts have been committed in determining the mechanisms of resistance with a view to both predicting which patients will become refractory to treatment and to developing new treatments and combinations to circumvent resistance. Alterations in the targeted protein node comprising CDK4/6, cyclin D and retinoblastoma, as well as alterations in upstream pathways that regulate the node and downstream effectors of transcription factor E2F, that execute the cell cycle regulation, have been affirmed as culprits in resistance development. A prominent downstream target of E2F that is repeatedly discussed in several studies is cyclin E. Conclusions: Key resistance mechanisms interfering with CDK4/6 inhibitor efficacy have been identified but are not yet used clinically. Diverse resistance mechanisms observed in individual cases would require individualized approaches to re-sensitize cancer cells and patients to cell cycle inhibition.
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Registered trials
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