Nuclear protein in testis (NUT) carcinoma, also known as NUT midline carcinoma, is a rare and highly aggressive malignancy associated with rearrangement of the NUT midline carcinoma family member 1 (NUTM1) gene located on chromosome 15q. First described in 1991, cases have predominantly occurred in midline structures of the head and neck and mediastinum, leading to its initial classification as midline carcinoma. However, NUT carcinoma can also arise in other organs of the body, including the lungs, bones, nasal cavity, salivary glands, central nervous system, and soft tissues, prompting the World Health Organization to rename midline carcinoma as "NUT carcinoma."

Clinical manifestations and imaging, as well as histopathological morphological features of NUT carcinoma, lack specificity. The clinical diagnosis primarily relies on immunohistochemical detection of NUT overexpression in the nucleus, or confirmation of NUTM1 gene (15q14) rearrangement or fusion with common partner genes through fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS). However, solely relying on NUT-positive immunohistochemistry or FISH may mistakenly diagnose certain tumors with NUTM1 rearrangement as NUT carcinoma. Some studies suggest that BET inhibitors may have limited efficacy for patients carrying gene fusions that are not dependent on BRD4. High-throughput sequencing is recommended to actively identify NUTM1 fusion partners to ensure accurate diagnosis, which also aids in prognostication and selection of subsequent drug therapies for NUT carcinoma patients. Our team is developing probes targeting specific fusion partners, and upon successful development, this will significantly reduce the diagnostic cost for NUT carcinoma fusion partners.

NUT carcinoma can occur at any age but is primarily diagnosed in young individuals. It is highly invasive, often diagnosed at an advanced stage with distant metastases, leading to poor prognosis. The prognosis is closely associated with factors such as NUTM1 fusion partners. Radiation therapy and chemotherapy have limited efficacy, with rapid disease progression observed in many cases. Current research suggests that bromodomain and extra terminal domain inhibitors (BETi) and histone deacetylase inhibitors (HDACi) hold promise as novel therapeutic approaches for NUT carcinoma. Our team is conducting a phase II clinical trial of the BET inhibitor NHWD-870 HCl. Since the establishment of the specialized NUT carcinoma clinic in China 10 months ago, we have treated nearly 90 patients with NUT carcinoma.