NSD3 (Nuclear Receptor Binding SET Domain Protein 3)

PRAME is highly and frequently expressed in NUT carcinoma, and the most common oncoprotein causing NUT carcinoma, BRD4::NUTM1, contributes to these high PRAME levels. PRAME epitopes presented by HLA class I are a previously unrecognized therapeutic vulnerability for NUT carcinoma that warrants clinical trials testing PRAME-targeted immunotherapies in this neglected patient population.

Additionally, NSD3 depletion also induced apoptosis and hindered cell proliferation, accompanied by altered expression of genes involved in these pathways. Our findings uncover a previously undescribed role of histone methyltransferase NSD3 in regulating human erythropoiesis.

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.

These intrinsic dynamical differences influence the number and stability of accessible binding modes, with BRD3 showing greater plasticity and weaker binding, particularly for NSD3. Our findings support a model in which local sequence variation tunes conformational selection and induced fit mechanisms, offering a structural rationale for paralog-specific targeting of BET proteins.

This large single-center series confirms that HNNC exhibits marked morphological heterogeneity and poor prognosis. Accurate diagnosis relies on immunohistochemistry, with FISH and RNA sequencing as needed, offering molecular insights to guide prognosis and clinical management.

P2, N=13, Recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Nov 2025 --> Nov 2026 | N=25 --> 13 | Trial completion date: Nov 2025 --> Nov 2026

NSD3::NUTM1 translocation might be more systematically sought in locally advanced PDTC/ATC with no point DNA mutations or other rearrangements. This strategy would better identify these patients, whose pathological diagnosis and clinical management may be challenging.

In human OS, NSD3 overexpression is seen in patient tumors and predicts a poor clinical outcome. Our study uncovers the crucial epigenetic dysregulation of histone lysine methyltransferase in osteosarcoma, opening new possibilities for therapy with epigenetic drugs.

In addition, novel strategies such as protein degradation via PROTACs and dual-target inhibitors are discussed. By systematically summarizing recent advances, this review seeks to facilitate and accelerate the development of effective NSD modulators, ultimately advancing therapeutic options for diseases driven by NSD dysregulation.

Our study highlights the clinical relevance of NSD3 amplification in LUSC through patient tissue analyses. These findings emphasize the potential of NSD3 as a prognostic biomarker and therapeutic target, bridging the gap between preclinical research and clinical application.

This study is the first phosphoproteomic investigation of FMC, highlighting the interactions of relevant phosphoproteins with other proteins and chemotherapy drugs associated with both feline and human mammary cancers. The findings provide valuable insights for the identification of diagnostic and prognostic biomarkers and potential therapeutic targets in cats with mammary carcinoma.

Although EGFR L858R mutation was detected throughout the transformation, genomic analyses were performed during the disease course, revealing the amplification of FGFR1 and NSD3, which have recently been proposed as potential driver oncogenes in lung squamous cell carcinoma. This case report highlights the genomic alterations observed in repeatedly biopsied specimens, along with a review of the relevant literature.