ArticleNature communications2021
Inhibition of CK1ε potentiates the therapeutic efficacy of CDK4/6 inhibitor in breast cancer.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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
37 citing papers in PubMed, 48 citations in OpenAlex.
- RAS P21 Protein Activator 3 finetunes Type I immunity by limiting HCK-mediated STAT4 phosphorylation.Nature communications · 2026Article
- Alternative Splicing in Cyclin-Dependent Kinase 4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer.Drug development research · 2026Review
- Review
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- MKRN2 enhances hepatocellular carcinoma proliferation through the p38 MAPK pathway.Human cell · 2026Article
- Bulky PP1 analogs exert cellular effects independently from analog-sensitive kinase inhibition.Frontiers in chemistry · 2026Article
- BET Bromodomain Inhibition Reverses CDK4/6 Inhibitor Resistance in Estrogen Receptor-Positive Breast Cancer via Induction of miR-34a-5p.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Decoding breast cancer: insights into molecular pathways & therapeutic approaches.Discover oncology · 2025Review
- Article
- In Silico Identification of 2,4-Diaminopyrimidine-Based Compounds as Potential CK1ε Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Triple Combination of MEK, BET, and CDK Inhibitors Significantly Reduces Human Malignant Peripheral Nerve Sheath Tumors in Mouse Models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Targeting CDK4/6 in breast cancer.Experimental & molecular medicine · 2025Review
- Using bioinformatics and artificial intelligence to map the cyclin-dependent kinase 4/6 inhibitor biomarker landscape in breast cancer.Future oncology (London, England) · 2024Review
- The GScience advances · 2024Article
- Overcoming ABCB1 mediated multidrug resistance in castration resistant prostate cancer.Cell death & disease · 2024Article
- APC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- CDKL3 is a targetable regulator of cell cycle progression in cancers.The Journal of clinical investigation · 2024Article
- Casein Kinase 1α-A Target for Prostate Cancer Therapy?Cancers · 2024Review
- Genome-wide in vivo CRISPR screen identifies TGFβ3 as actionable biomarker of palbociclib resistance in triple negative breast cancer.Molecular cancer · 2024Article
- Reciprocal antagonism of PIN1-APC/CNature communications · 2024Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Although inhibitors targeting CDK4/6 kinases (CDK4/6i) have shown promising clinical prospect in treating ER+/HER2- breast cancers, acquired drug resistance is frequently observed and mechanistic knowledge is needed to harness their full clinical potential. Here, we report that inhibition of CDK4/6 promotes βTrCP1-mediated ubiquitination and proteasomal degradation of RB1, and facilitates SP1-mediated CDK6 transcriptional activation. Intriguingly, suppression of CK1ε not only efficiently prevents RB1 from degradation, but also prevents CDK4/6i-induced CDK6 upregulation by modulating SP1 protein stability, thereby enhancing CDK4/6i efficacy and overcoming resistance to CDK4/6i in vitro. Using xenograft and PDX models, we further demonstrate that combined inhibition of CK1ε and CDK4/6 results in marked suppression of tumor growth in vivo. Altogether, these results uncover the molecular mechanisms by which CDK4/6i treatment alters RB1 and CDK6 protein abundance, thereby driving the acquisition of CDK4/6i resistance. Importantly, we identify CK1ε as an effective target for potentiating the therapeutic efficacy of CDK4/6 inhibitors.
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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.