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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
NUT carcinoma is a fast-growing cancer of the midline of the body driven by a single fused gene, BRD4-NUTM1, that locks cells in an immature state. Chemotherapy and surgery rarely control it for long, but drugs that block the BET proteins the fusion depends on have produced responses and are the focus of trials.
NUT carcinoma is a poorly differentiated squamous carcinoma defined by rearrangement of NUTM1 (nuclear protein in testis), most often fused to BRD4 (about 70 percent), otherwise BRD3, NSD3 or ZNF532. The fusion protein tethers NUT's histone acetyltransferase-recruiting domain to BET bromodomains, creating megadomains of hyperacetylated chromatin that drive MYC and SOX2 expression and block squamous differentiation. It was first recognised in the mediastinum of children and young adults but occurs at any age and in the sinonasal tract, lung, and other sites; diagnosis requires NUT immunohistochemistry (highly specific) or fusion testing, and many cases were historically misdiagnosed as undifferentiated carcinoma or sarcoma.
The disease is among the most aggressive human cancers. Multimodality treatment (surgery, radiotherapy and ifosfamide- or platinum-based chemotherapy, Ewing-type regimens) achieves control in a minority, mostly those with localised disease amenable to complete resection and radiotherapy. The International NUT Carcinoma Registry (Brigham and Women's Hospital) has pooled outcomes and shown that initial resection or radiotherapy is associated with longer survival, and that non-BRD4 fusions have a somewhat better course.
| Setting | Approach | Guideline |
|---|---|---|
| Localised | Multimodality: complete resection where feasible, radiotherapy, and intensive chemotherapy (ifosfamide-based or platinum-based, often Ewing-type regimens); early referral to a centre with NUT carcinoma experience. | not mapped |
| Advanced or relapsed | Clinical trial of a BET inhibitor (ZEN-3694, NUV-868, molibresib) alone or with chemotherapy; palliative chemotherapy and radiotherapy. | not mapped |