^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    GENE:

    NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

    i
    Other names: NSD2, Nuclear Receptor Binding SET Domain Protein 2, MMSET, KMT3G, WHSC1, Histone-Lysine N-Methyltransferase NSD2, Nuclear SET Domain-Containing Protein 2, Wolf-Hirschhorn Syndrome Candidate 1, TRX5, Multiple Myeloma SET Domain Containing Protein Type III, Probable Histone-Lysine N-Methyltransferase NSD2, Multiple Myeloma SET Domain Containing Protein, Multiple Myeloma SET Domain-Containing Protein, Wolf-Hirschhorn Syndrome Candidate 1 Protein, IL5 Promoter REII Region-Binding Protein, Trithorax/Ash1-Related Protein , Protein Trithorax-5, KIAA1090, REIIBP, KMT3F, RAUST, WHS
    Associations

    News

    Trials
    2d
    Genetic loss of CHD1 regulates distinct histone post-translational modifications in the development of castration-resistant prostate cancer. (PubMed, Neoplasia)
    Notably, this CHD1-deficient epigenetic state confers resistance to NSD2 inhibition. These findings highlight a previously unrecognized role in tumor resistance for CHD1 in modulating HMEs that may influence lineage plasticity as well as suggest new avenues for personalized therapeutic strategies targeting CHD1-specific epigenetic vulnerabilities.
    Journal
    |
    CHD1 (Chromodomain Helicase DNA Binding Protein 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    3d
    NCI-2023-03181: Glofitamab With Obinutuzumab, Venetoclax, and Lenalidomide for the Treatment of Patients With Newly Diagnosed High Risk Mantle Cell Lymphoma (clinicaltrials.gov)
    P1/2, N=50, Recruiting, City of Hope Medical Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • SOX11 (SRY-Box Transcription Factor 11) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    TP53 mutation • Chr t(11;14)
    |
    Venclexta (venetoclax) • lenalidomide • Gazyva (obinutuzumab) • Columvi (glofitamab-gxbm)
    14d
    Potential role of circ_WHSC1 and miR-145-5p in breast cancer promotion. (PubMed, Biochem Biophys Rep)
    Cumulatively, circ_WHSC1/miR-145-5p can be suggested as a potential molecular axis contributing to the pathogenesis of breast cancer. However, further functional assays are needed to validate this hypothesis.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • MIR145 (MicroRNA 145) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    HER-2 negative
    16d
    Ibrutinib in Treating Participants With Untreated High Risk Smoldering Mantle Cell Lymphoma (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Feb 2026 --> Feb 2028
    Trial completion date • Trial primary completion date
    |
    TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    TP53 mutation • CD20 positive • TP53 wild-type
    |
    Imbruvica (ibrutinib)
    22d
    Glofitamab Plus Ibrutinib With Obinutuzumab for the Treatment of Patients With Mantle Cell Lymphoma, IGNITE MCL Trial (clinicaltrials.gov)
    P1/2, N=27, Recruiting, OHSU Knight Cancer Institute | Not yet recruiting --> Recruiting
    Enrollment open
    |
    TP53 (Tumor protein P53) • CD20 (Membrane Spanning 4-Domains A1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • KMT2D (Lysine Methyltransferase 2D) • NOTCH2 (Notch 2) • PAX5 (Paired Box 5) • CD4 (CD4 Molecule) • CD5 (CD5 Molecule) • SOX11 (SRY-Box Transcription Factor 11) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    TP53 mutation • Chr del(17p) • Chr t(11;14) • CDKN2A deletion
    |
    Imbruvica (ibrutinib) • Gazyva (obinutuzumab) • Columvi (glofitamab-gxbm)
    1m
    Targeting epithelial-mesenchymal transition and apoptosis: novel histone methyltransferase inhibitors for colon cancer suppression. (PubMed, Bioorg Med Chem)
    Finally, non-cancerous human cell lines and the zebrafish embryotoxicity model were utilized for the evaluation of the drug safety of DHT-07343 and DHT-07171. In conclusion, our study demonstrated that DHT-07343 and DHT-07171 could be promising HMT inhibitors that exhibit anti-cancer activities by suppressing cell proliferation and migration, providing a potential strategy for colon cancer therapy.
    Journal
    |
    NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    2ms
    RVd and CyBorD therapies remodel B-cell maturation signaling and alter immune and clonal architecture in multiple myeloma. (PubMed, Cancer Biol Ther)
    Although lenalidomide/bortezomib/dexamethasone (RVd) and cyclophosphamide/bortezomib/dexamethasone (CyBorD) are clinically effective, their precise impacts on PC/B-cell maturation remain unclear. RVd responders further downregulated CD56, CD269, and CD329, and increased CD243. These shared and divergent modulations elucidate the molecular underpinnings of RVd and CyBorD efficacy and inform precision regimen selection.
    Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • NOTCH1 (Notch 1) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • TNFRSF17 (TNF Receptor Superfamily Member 17) • RARA (Retinoic Acid Receptor Alpha) • ABCG2 (ATP Binding Cassette Subfamily G Member 2) • PAX5 (Paired Box 5) • KLF4 (Kruppel-like factor 4) • NCAM1 (Neural cell adhesion molecule 1) • SDC1 (Syndecan 1) • CD200 (CD200 Molecule) • IRF4 (Interferon regulatory factor 4) • CD52 (CD52 Molecule) • PRDM1 (PR/SET Domain 1) • NANOG (Nanog Homeobox) • NES (Nestin) • XBP1 (X-box-binding protein 1) • CD81 (CD81 Molecule) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2) • SLAMF7 (SLAM Family Member 7) • SIGLEC9 (Sialic Acid Binding Ig Like Lectin 9)
    |
    lenalidomide • bortezomib • cyclophosphamide
    2ms
    Targeting nuclear receptor-binding SET domain protein 2 (NSD2) for cancer therapy: Challenges and emerging strategies. (PubMed, Bioorg Chem)
    Specifically, these small molecules are classified and elaborated based on their structural characteristics; for each structural category, the binding modes, structural features, and pharmacological activities of typical compounds are analyzed in detail, while their inherent advantages and limitations are critically evaluated. Collectively, this review offers valuable insights and guidance for the future research and development of safer, more effective, and more targeted NSD2 small-molecule agents.
    Review • Journal
    |
    NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    3ms
    EXPRESSION OF CONCERN: CircWHSC1 Serves as a Prognostic Biomarker and Promotes Malignant Progression of Non-Small-Cell Lung Cancer Via miR-590-5p/SOX5 Axis. (PubMed, Environ Toxicol)
    In the absence of the original data, the journal and publisher are unable to fully investigate the discrepancies. Therefore, the journal has decided to issue an Expression of Concern to inform and alert readers.
    Clinical • Retrospective data • Review • Journal
    |
    NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    3ms
    NSD Family-Mediated H3K36 Methylation in Human Cancer: Mechanisms and Therapeutic Opportunities. (PubMed, Biomedicines)
    Pharmacological inhibition of NSD catalytic activity, as well as alternative approaches such as targeted protein degradation or disruption of cofactor interactions, are emerging as promising therapeutic strategies for cancer treatment. This review summarizes the structural features, molecular functions, and cancer-associated alterations and mechanisms of the NSD family and highlights recent advances in targeting these enzymes as potential epigenetic vulnerabilities in cancer.
    Review • Journal
    |
    NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • NSD3 (Nuclear Receptor Binding SET Domain Protein 3) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    3ms
    NSD2 targeting reverses plasticity and drug resistance in prostate cancer. (PubMed, Nature)
    Pharmacological inhibition of NSD2 with a first-in-class small molecule reverses plasticity and synergizes with enzalutamide to suppress growth and promote cell death in human patient-derived organoids of multiple CRPC subtypes in culture and in xenografts. Co-targeting of NSD2 and AR may represent a new therapeutic strategy for lethal forms of CRPC that are currently recalcitrant to treatment.
    Journal
    |
    NSD2 (Nuclear Receptor Binding SET Domain Protein 2)
    |
    Xtandi (enzalutamide)