ArticleCancers2020
Combined CDK2 and CDK4/6 Inhibition Overcomes Palbociclib Resistance in Breast Cancer by Enhancing Senescence.
Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
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
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 147 citations in OpenAlex.
- Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer.JCO precision oncology · 2022Pooled it
- Molecular signatures of triple-negative breast cancer cells acquiring palbociclib resistance via continuous exposure.Oncology letters · 2026Article
- Article
- TP53 mutation is associated with shorter treatment duration with CDK4/6 inhibitors, but not with immune checkpoint inhibitors, in ER-positive/HER2-negative breast cancer: real-world perspective.Breast cancer research : BCR · 2026Article
- Cell-cycle targeted cancer therapy: clinical advances, biological gaps, and the emergence of selective CDK4 inhibitors.Journal of hematology & oncology · 2026Review
- Emerging Strategies to Inhibit the G1/S Transition for Cancer Therapy.Cancer research · 2026Review
- Kinase Inhibitors for Targeted Cancer Therapy.Current topics in medicinal chemistry · 2026Review
- Article
- CDK2 inhibition enhances CDK4/6 inhibitor antitumor activity in comprehensive breast cancer PDX model screen.NPJ breast cancer · 2025Article
- Genomics-led approach to drug testing in models of undifferentiated pleomorphic sarcoma.Molecular oncology · 2025Article
- Therapeutic benefits of maintaining CDK4/6 inhibitors and incorporating CDK2 inhibitors beyond progression in breast cancer.bioRxiv : the preprint server for biology · 2025Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- IL-6 predicts CDK4/6 inhibitor resistance, identifying STAT3 as a target in HR + /HER2-negative metastatic breast cancer.NPJ precision oncology · 2025Article
- Molecular Mechanisms and Therapeutic Strategies to Overcome Resistance to Endocrine Therapy and CDK4/6 Inhibitors in Advanced ER+/HER2- Breast Cancer.International journal of molecular sciences · 2025Review
- Profiling the Activity of the Potent and Highly Selective CDK2 Inhibitor BLU-222 Reveals Determinants of Response in CCNE1-Aberrant Ovarian and Endometrial Tumors.Cancer research · 2025Article
- Targeting cyclin-dependent kinase 2 (CDK2) interactions with cyclins and Speedy 1 (Spy1) for cancer and male contraception.Future medicinal chemistry · 2025Review
- Targeting CDK4/6 in breast cancer.Experimental & molecular medicine · 2025Review
- Kinome-Focused CRISPR-Cas9 Screens in African Ancestry Patient-Derived Breast Cancer Organoids Identify Essential Kinases and Synergy of EGFR and FGFR1 Inhibition.Cancer research · 2025Article
- Correlation of senescence-related gene FEN1 on neuroblastoma progression and cisplatin chemotherapy sensitivity.Oncology research · 2025Article
- Genome-wide CRISPR screen identified NEK6 as a determinant of sensitivity to CDK4/6 inhibitor in endometrial cancer.Frontiers in pharmacology · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Breast cancer represents the number one global cancer burden in women and the hormone receptor (HR)-positive subtype comprises approximately 70% of breast cancers. Unfortunately, acquired resistance ultimately occurs in almost all cases, even though cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are a highly effective therapy for HR-positive/human epidermal growth factor receptor 2-negative subtype. Here, we investigated mechanisms of resistance to CDK4/6 inhibitor and potential therapeutic strategies using our palbociclib-resistant preclinical model. We observed that cyclin E was significantly overexpressed in palbociclib-resistant cells, and similar association was also confirmed in pleural effusion samples collected from HR-positive breast cancer patients. After confirmation of cyclin E-CDK2 interaction by co-immunoprecipitation, we demonstrated CDK2 inhibition combined with palbociclib synergistically suppressed proliferation of palbociclib-resistant cells and growth of palbociclib-resistant xenograft in mice. We also proved that enhancing C-MYC-mediated senescence is a novel mechanism behind the synergism created by targeting both CDK2 and CDK4/6. Furthermore, the clinical relevance of cyclin E as a therapeutic target was supported by significant association between CCNE1 overexpression and poor prognosis based on large-scale public gene expression data sets in HR-positive breast cancer patients. Therefore, we propose cyclin E-CDK2 signaling as a promising therapeutic target for overcoming cyclin E-associated resistance to CDK4/6 inhibitor.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.