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    GENE:

    CDK4 (Cyclin-dependent kinase 4)

    i
    Other names: CDK4, PSK-J3, Cyclin-dependent kinase 4
    2d
    Mucosal melanoma: clinicopathological, molecular and prognostic features in a retrospective cohort. (PubMed, Virchows Arch)
    NRAS was the most frequent mutation, followed by ARID1A, CDK4, CDKN2A, JAK2 and MYC, without a significant association with survival. These results emphasise the prognostic value of mitotic index and surgical completeness, while confirming the marked molecular heterogeneity of mucosal melanoma and the lack of a single dominant actionable alteration.
    Retrospective data • Journal
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    NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • JAK2 (Janus kinase 2) • CDK4 (Cyclin-dependent kinase 4)
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    ARID1A mutation
    3d
    BMX inhibition overcomes small cell lung cancer chemoresistance by stabilizing E2F1 via ERK1/2-Cyclin D1/CDK4/6 axis. (PubMed, Signal Transduct Target Ther)
    E2F1 knockdown decreased the expression of genes associated with cell cycle regulation, migration, invasion, and DNA repair, further sensitizing chemoresistant SCLC cells to cisplatin...In vivo xenograft models demonstrated that the combination significantly inhibited tumor growth without causing significant toxicity. Our findings reveal the molecular mechanisms of SCLC chemoresistance and suggest potential therapeutic strategies targeting the BMX-E2F1 axis to overcome this challenge.
    Journal
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    CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • E2F1 (E2F transcription factor 1)
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    cisplatin
    3d
    Adenocarcinoma of Mammary Gland Type of the Vulva. (PubMed, Int J Surg Pathol)
    Given the rarity of the tumor, it is crucial to distinguish it from morphological mimics to inform appropriate patient management. Treatment approaches are typically based on protocols for primary breast cancer, given the histological and biological similarities between these tumors and breast tissue.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PGR (Progesterone receptor) • AR (Androgen receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • KRT7 (Keratin-7) • TP63 (Tumor protein 63) • GATA3 (GATA binding protein 3) • TRPS1 (Transcriptional Repressor GATA Binding 1)
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    HER-2 amplification • TP53 Y220C
    8d
    FIH Study of RGT-419B Alone and With Endocrine Therapy in HR-Positive, HER2-Negative Advanced/Metastatic Breast Cancer (clinicaltrials.gov)
    P1, N=64, Recruiting, Regor Pharmaceuticals Inc. | Trial completion date: Sep 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Sep 2026
    Trial completion date • Trial primary completion date • First-in-human
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
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    HER-2 negative
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    RG6794
    9d
    Alpelisib and Fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the German PRAEGNANT trial. (PubMed, Breast Cancer Res Treat)
    This prospective real-world analysis shows slightly shorter median PFS and OS times compared with the pivotal trials. Patients in our analyses received alpelisib in later therapy lines, which may explain the poorer outcome.
    Journal
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    HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDK4 (Cyclin-dependent kinase 4)
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    HER-2 positive • HR positive • HER-2 negative • PIK3CA mutation • EGFR positive • HR positive + HER-2 negative
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    Piqray (alpelisib) • fulvestrant
    9d
    SOLTI-2101: Advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer (2023-508828-35-01)
    P2/3, N=316, Completed, Solti Group | Active, not recruiting --> Completed
    Trial completion
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CDK4 (Cyclin-dependent kinase 4)
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    ER positive • HR positive • HER-2 negative • HR positive + HER-2 negative • HER-2 negative + ER positive
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    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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    Ibrance (palbociclib) • Tevimbra (tislelizumab-jsgr) • Kisqali (ribociclib)
    10d
    SNHG10 promotes tumorigenesis through the EGFR/AKT/ERK/mTOR and miR-150-5p/VEGF-A axis, along with gemcitabine resistance in pancreatic ductal adenocarcinoma. (PubMed, Cell Death Discov)
    Silencing of SNHG10 decreases cell survival, proliferation, clonogenicity, EMT tumor growth through the EGFR/AKT/ERK/mTOR axis, and restores the expression of miR-150-5p, which eventually downregulates VEGF-A. SNHG10 downregulation enhanced the gemcitabine sensitivity in gemcitabine-resistant PDAC cells.
    Journal
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    EGFR (Epidermal growth factor receptor) • MET (MET proto-oncogene, receptor tyrosine kinase) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDH1 (Cadherin 1) • BIRC5 (Baculoviral IAP repeat containing 5) • CDK6 (Cyclin-dependent kinase 6) • AURKA (Aurora kinase A) • VIM (Vimentin) • AURKB (Aurora Kinase B) • CDH2 (Cadherin 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CCNB1 (Cyclin B1) • MIR150 (MicroRNA 150) • SNHG10 (Small Nucleolar RNA Host Gene 10)
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    gemcitabine
    10d
    Unlocking nature's cure: utilizing Indian and Chinese medicinal plants as CDK inhibitors in the p53 pathway of breast cancer. (PubMed, In Silico Pharmacol)
    Top docked complexes, such as CDK1-Michelalbine (Indian) and CDK1-Emodin (Chinese), alongside CDK1-Doxorubicin (conventional), were subjected to Molecular Dynamic Simulation for comparative analysis...This comprehensive in-silico approach uncovers potential novel therapeutic options for targeting CDKs in breast cancer. The online version contains supplementary material available at 10.1007/s40203-026-00613-8.
    Journal
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    CDK4 (Cyclin-dependent kinase 4) • CDK6 (Cyclin-dependent kinase 6) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1)
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    TP53 mutation
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    doxorubicin hydrochloride
    10d
    Membrane protein-focused CRISPR screen identifies ATP2A2 as a druggable transcriptional co-regulator of CCND1 (cyclin D1) in lung adenocarcinoma. (PubMed, Life Sci)
    This study revealed ATP2A2-HACD3-NF-κB as a regulatory axis of cyclin D1 expression and shed light on developing ATP2A2-targeted medications for LUAD treatment.
    Journal
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    CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4)
    11d
    LEAH: Cohort Evaluation of Body Fluids Early Detection of Cancer in High-risk Individuals (clinicaltrials.gov)
    P=N/A, N=5909, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting
    Enrollment open
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • RUNX1 (RUNX Family Transcription Factor 1) • BAP1 (BRCA1 Associated Protein 1) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • CDH1 (Cadherin 1) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • RAD51D (RAD51 paralog D) • DDX41 (DEAD-Box Helicase 41) • GATA2 (GATA Binding Protein 2) • DICER1 (Dicer 1 Ribonuclease III) • FLCN (Folliculin) • PRSS1 (Serine Protease 1) • SDHD (Succinate Dehydrogenase Complex Subunit D) • TXNIP (Thioredoxin Interacting Protein) • ANKRD26 (Ankyrin Repeat Domain Containing 26) • BMPR1A (Bone Morphogenetic Protein Receptor Type 1A) • HOXB13 (Homeobox B13)
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    TP53 mutation • PTEN deletion
    13d
    Expanding the molecular grading criteria in IDH-mutant astrocytoma. (PubMed, Neuro Oncol)
    The presence of CDK4, CCND2, PDGFRA, PIK3R1, MYCN, and EGFR alterations result in an intermediate patient survival in IDH-mutant astrocytoma. Adding these molecular alterations should be considered in future diagnostic classification systems to improve stratification of high-risk patients.
    Journal
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    EGFR (Epidermal growth factor receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CCND2 (Cyclin D2)
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    EGFR mutation • PIK3CA mutation • EGFR amplification • CDKN2A deletion • MYCN amplification • PDGFRA mutation
    13d
    Design and synthesis of novel 1,2,4-triazolobenzene sulfonamide derivatives as selective CDK1 inhibitors with potent in vivo anticancer efficacy. (PubMed, Eur J Med Chem)
    In vivo efficacy evaluation demonstrated that 30 mg/kg 11l achieved a tumor growth inhibition (TGI) rate of 56.4%, without inducing significant body weight loss or observable organ toxicity. Collectively, these findings identify 11l as a safe CDK1 inhibitor with a distinct mechanism of action, supporting its potential as a promising therapeutic strategy for cancer treatment.
    Preclinical • Journal
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    CDK4 (Cyclin-dependent kinase 4) • CDK2 (Cyclin-dependent kinase 2) • CDK1 (Cyclin-dependent kinase 1) • CCNB1 (Cyclin B1) • CDC45 (Cell Division Cycle 45)