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    BIOMARKER:

    NOTCH4 mutation

    i
    Other names: NOTCH4, INT3, Neurogenic Locus Notch Homolog Protein 4, Notch Homolog 4
    Entrez ID:
    4855
    Related biomarkers:
    Expression
    Mutation
    Others
    over1year
    NOTCH4 sensitizes lung adenocarcinomas to EGFR-TKIs through transcriptional down-regulation of HES1. (PubMed, Nat Commun)
    Moreover, inhibition of the NOTCH4-HES1 pathway using inhibitors and siRNAs abolishes the resistance of EGFR-TKI. Overall, we report that the NOTCH4 mutation sensitizes LUAD patients to EGFR-TKIs through transcriptional down-regulation of HES1 and that targeted blockade of this signaling cohort could reverse EGFR-TKI -resistance in LUAD, providing a potential approach to overcome resistance to EGFR-TKI -therapy.
    Journal
    |
    STAT3 (Signal Transducer And Activator Of Transcription 3) • CD4 (CD4 Molecule) • NOTCH4 (Notch 4) • HES1 (Hes Family BHLH Transcription Factor 1)
    |
    EGFR mutation • EGFR expression • NOTCH4 mutation
    over2years
    NOTCH4 mutation as predictive biomarker for immunotherapy benefits in NRAS wildtype melanoma. (PubMed, Front Immunol)
    Gene set enrichment analysis revealed NOTCH4-Mut tumor enhanced anti-tumor immunity. NOTCH4 mutation may promote tumor immunity and serve as a biomarker to predict good immune response in NRAS wildtype melanoma and guide immunotherapeutic responsiveness.
    Journal • Tumor Mutational Burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH4 (Notch 4)
    |
    NRAS mutation • RAS wild-type • NRAS wild-type • NOTCH mutation • NOTCH4 mutation
    over2years
    NOTCH4 mutation as a potential predictive biomarker for immunotherapy in NRAS wildtype melanoma. (ASCO 2022)
    NOTCH4 mutation may promote tumor immunity and serve as a biomarker to predict good immune response in NRAS wildtype melanoma and guiding immunotherapeutic responsiveness.
    Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NOTCH1 (Notch 1) • CD8 (cluster of differentiation 8) • IFNG (Interferon, gamma) • CD4 (CD4 Molecule) • NOTCH4 (Notch 4)
    |
    PD-L1 expression • NRAS mutation • NOTCH1 mutation • RAS wild-type • NRAS wild-type • NOTCH mutation • NOTCH4 mutation
    almost3years
    Investigation of NOTCH mutation and correlation with immunotherapy biomarker in Chinese colorectal cancer patients (AACR 2022)
    The results showed that the NOTCH genes had a high correlation with TMB and MSI in CRC, and the NOTCH3 might a potential biomarker for immune checkpoint therapy.
    Clinical • Tumor mutational burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NOTCH1 (Notch 1) • NOTCH2 (Notch 2) • NOTCH3 (Notch Receptor 3) • NOTCH4 (Notch 4)
    |
    PD-L1 expression • TMB-H • NOTCH1 mutation • NOTCH mutation • NOTCH4 mutation
    |
    PD-L1 IHC 22C3 pharmDx
    over3years
    Identification of NOTCH4 mutation as a response biomarker for immune checkpoint inhibitor therapy. (PubMed, BMC Med)
    Our findings indicated that NOTCH4 mutation serves as a novel biomarker correlated with a better response to ICI therapy.
    Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • NOTCH4 (Notch 4)
    |
    TMB-H • NOTCH4 mutation
    over3years
    Comprehensive molecular profiling of pulmonary pleomorphic carcinoma. (PubMed, NPJ Precis Oncol)
    Primary and metastatic tumors shared oncogenic mutations among genes such as KRAS and TP53, and additional alterations including NOTCH4 mutations were specifically identified in the metastatic regions. Our data suggest that therapies targeting activating driver mutations may be effective for patients with PPC and that immune checkpoint inhibitors of PPC may be recommended after careful assessment of PD-L1 expression in each epithelial and sarcomatoid component.
    Journal • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NOTCH4 (Notch 4)
    |
    PD-L1 expression • TP53 mutation • KRAS mutation • EGFR mutation • PD-L1 overexpression • MET mutation • NOTCH4 mutation
    4years
    Comprehensive genomic profile of Chinese lung cancer patients and mutation characteristics of individuals resistant to icotinib/gefitinib. (PubMed, Sci Rep)
    EGFR amplification was commonly detected in patients with acquired lcotinib/gefitinib resistance. DNMT3A and NOTCH4 mutations may be associated with the benefit of icotinib/gefitinib treatment.
    Clinical • Journal • Tumor Mutational Burden
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR1 (Fibroblast growth factor receptor 1) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • PBRM1 (Polybromo 1) • KMT2D (Lysine Methyltransferase 2D) • LRP1B (LDL Receptor Related Protein 1B) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KMT2C (Lysine Methyltransferase 2C) • FAT1 (FAT atypical cadherin 1) • AURKA (Aurora kinase A) • NOTCH4 (Notch 4)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • NRAS mutation • PIK3CA mutation • HER-2 mutation • EGFR amplification • STK11 mutation • DNMT3A mutation • NF1 mutation • ALK mutation • KEAP1 mutation • CDKN2A mutation • PBRM1 mutation • NOTCH4 mutation
    |
    gefitinib • Conmana (icotinib)