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    GENE:

    MDM4 (The mouse double minute 4)

    i
    Other names: MDM4, The mouse double minute 4, MDM4 Regulator Of P53, Mdm2-Like P53-Binding Protein, MDM4, P53 Regulator, Double Minute 4, Human Homolog Of; P53-Binding Protein, P53-Binding Protein Mdm4, Double Minute 4 Protein
    7d
    Synergistic antitumor effect of oroxylin A and donafenib in hepatocellular carcinoma through tumor protein p53 signaling pathway activation. (PubMed, World J Gastroenterol)
    Oroxylin A and donafenib exert a synergistic anti-tumor effect in HCC by co-activating the TP53 signaling pathway through distinct but complementary molecular axes. This combination strategy presents a promising and viable therapeutic approach to overcome the limitations of donafenib monotherapy in the treatment of HCC.
    Journal
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    MDM4 (The mouse double minute 4) • CDK9 (Cyclin Dependent Kinase 9)
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    Zepsun (donafenib)
    1m
    Combined inhibition of FACT and BET disrupts transcription to suppress tumor growth in mouse models of diffuse midline glioma. (PubMed, Sci Transl Med)
    In vitro, a combinatorial therapeutic approach using the FACT inhibitor CBL0137, coupled with BET inhibition, revealed potent and synergistic cytotoxicity across a range of DMG cultures...This combination also elicited immune-related effects, including activation of the interferon response and antigen presentation mechanisms in DMG cells and induction of an activated state in macrophages and T cells, as demonstrated in an immunocompetent setting with spatial transcriptomics. Together, our data highlight the therapeutic promise of simultaneously targeting FACT and BET proteins in DMG, offering a dual tumor-intrinsic and immune-mediated strategy for combating this devastating pediatric brain tumor.
    Preclinical • Journal
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    PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MDM4 (The mouse double minute 4) • SOX2 • BRD4 (Bromodomain Containing 4)
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    CBL0137
    2ms
    Immune therapy-related hyperprogressive disease: Molecular mechanisms, biomarkers, and clinical strategies. (PubMed, World J Clin Oncol)
    It further delves into biomarker-based predictive models, targeted combination therapy strategies, and salvage treatment alternatives. Ultimately, it puts forward future directions, including the establishment of a multicenter HPD registry database and organoid predictive models, aiming to offer evidence-based guidance for clinical practice.
    Review • Journal • IO biomarker
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    EGFR (Epidermal growth factor receptor) • MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4)
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    EGFR mutation
    2ms
    A Case of Multicentric Isocitrate Dehydrogenase-Wildtype Glioblastoma With Divergent Clonal Evolution. (PubMed, Cureus)
    Notably, most reported multicentric glioblastomas exhibit monoclonal driver mutations across lesions, suggesting a single origin. In the present case, the two tumors had different molecular signatures. This case underscores the importance of comprehensive genetic analysis of multicentric glioblastomas and highlights how divergent molecular pathologies can inform the prognosis and open opportunities for targeted treatment.
    Journal
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    EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • MDM4 (The mouse double minute 4)
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    BRAF V600E • EGFR mutation • BRAF V600 • EGFR amplification • CDKN2A deletion • IDH wild-type
    2ms
    A Complex Case of Retinoblastoma Solved by the Combined Approach of Humor/Plasma cfDNA-NGS and LR-WGS. (PubMed, Genes (Basel))
    This experience tells us that a combined approach with TSO500 Illumina NGS on cfDNA, along with LR-WGS, is able to help solve complex cases and define the appropriate treatment and surveillance strategy.
    Journal • Next-generation sequencing • BRCA Biomarker
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    ALK (Anaplastic lymphoma kinase) • BRCA2 (Breast cancer 2, early onset) • RB1 (RB Transcriptional Corepressor 1) • MDM4 (The mouse double minute 4)
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    TruSight Oncology 500 Assay
    2ms
    Genetic Variations in BCL3, MDM4, KLF14, and miR-146a and Their Associations with the Predisposition and Progression of Myeloproliferative Disorder and Chronic Myeloid Leukemia Patients. (PubMed, Mol Syndromol)
    In addition, we assessed the effect of gene polymorphisms on the course of the disease, and rapid disease progression was found to be correlated with the presence of these polymorphisms. These findings could help determine the risk of developing MPNs and patient prognosis.
    Journal
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    MDM4 (The mouse double minute 4) • BCL3 (BCL3 Transcription Coactivator) • KLF14 (KLF Transcription Factor 14)
    4ms
    The MDM4 Inhibitor CEP-1347 Activates Wild-type p53 in Ovarian Clear Cell Carcinoma Cells and Potently Inhibits their Growth. (PubMed, Anticancer Res)
    The present results suggest the potential of targeting MDM4 with CEP-1347 as a therapeutic approach for the treatment of OCCC with wild-type p53.
    Journal • P53WT
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    MDM4 (The mouse double minute 4) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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    TP53 mutation • TP53 wild-type
    4ms
    Senolytic Elimination of Senescent Ovarian Clear Cell Carcinoma Cells Induced by CEP-1347 With the BH3 Mimetic Navitoclax. (PubMed, Anticancer Res)
    CEP-1347 induced cellular senescence in OCCC cells with wild-type TP53. The combination of CEP-1347 with senolytics, such as navitoclax, represents a rational strategy to ensure the selective elimination of senescent OCCC cells and enhance therapeutic efficacy.
    Journal
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    MDM4 (The mouse double minute 4)
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    TP53 mutation • TP53 wild-type
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    navitoclax (ABT 263)
    5ms
    ALRN-6924 and Paclitaxel in Treating Patients With Advanced, Metastatic, or Unresectable Solid Tumors (clinicaltrials.gov)
    P1, N=35, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Jul 2025 --> Jul 2027 | Trial primary completion date: Jul 2025 --> Jul 2027
    Trial completion date • Trial primary completion date
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • MDM2 (E3 ubiquitin protein ligase) • MDM4 (The mouse double minute 4)
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    ER positive • HER-2 negative • TP53 wild-type
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    paclitaxel • sulanemadlin (ALRN-6924)
    5ms
    SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
    P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2027 --> Jun 2040 | Trial primary completion date: Dec 2026 --> Dec 2038
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • BRCA (Breast cancer early onset) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 mutation • AKT1 mutation