DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for NUT midline carcinoma — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNUT midline carcinoma maps to a 2-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for nut midline carcinoma is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
bromodomain containing 4 (BRD4) — BRD4 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet oxyethane-2,1-diyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6DNE · 2.958 Å · ligand N,N'-[ethane-1,2-diylbis(oxyethane-2,1-diyl)]bis{2-[(6S)-4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetamide} (H1V). Experimental structure, not a prediction.
What the evidence adds up to
NUT midline carcinoma is a poorly differentiated squamous cancer defined by rearrangement of the NUT gene. In a retrospective database of 63 patients, the largest cohort studied as of 2012, median overall survival was 6.7 months. Two-year progression-free survival was 9% (95% CI 1–17%), and two-year overall survival was 19% (95% CI 7–31%). Multivariate analysis indicated that extent of surgical resection and initial radiotherapy were independent predictors of progression-free and overall survival. No chemotherapeutic regimen was associated with improved outcome in that analysis.
Individual case reports describe responses to specific drugs. A 12-year-old girl showed partial response to cisplatin and docetaxel, then complete response to gemcitabine, and later partial response to vinorelbine; she died 89 weeks after onset. A patient with widely metastatic disease achieved remission lasting 37 months after compressed cycles of vincristine, cyclophosphamide, and doxorubicin alternating with ifosfamide and etoposide, combined with high-dose radiation and post-chemotherapy resection. Two cases of sinonasal NUT carcinoma treated with upfront surgery followed by adjuvant chemoradiation were reported as successful, without numerical survival data given.
A case of sinonasal NUT carcinoma treated with cisplatin, fluorouracil, docetaxel, and pembrolizumab in first line showed poor response; the patient died of disease progression 5.4 months after diagnosis. PD-L1 expression was 10% by tumour proportion score. The authors state that the efficacy of immunotherapy in NUT midline carcinoma is not known. A pericardial NUT carcinoma in a 2-year-old girl was partially resected; no treatment outcome was reported beyond the surgical finding.
What is still missing: prospective trials large enough to test any regimen, reliable biomarkers for patient stratification, and funding for a disease so rare that most evidence remains single-case reports.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical Cancer Research · 2012 · 413 citations · open access
Clinicopathologic Features and Long-term Outcomes of NUT Midline Carcinoma
AbstractPURPOSE: NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations. EXPERIMENTAL DESIGN: A clinical database was established using retrospective demographic and outcomes data available on all known cases of NMC. Questionnaires were completed by treating physicians. Pathologic, demographic, and clinical variables were assessed for 63 patients, the largest cohort of patients with NMC studied to date. Outcome data from 54 patients were available for survival analyses. RESULTS: The diagnosis of NMC has increased annually since 2007. Since 2009, there has been an observed increase in the age at diagnosis (P < 0.05). Geographic distribution of patients with NMC has been concentrated in the United States (n = 41, 65%). The median overall survival for patients with NMC was 6.7 months. The 2-year progression-free survival (PFS) was 9% with a 95% confidence interval (CI) of 1% to 17% [1-year PFS 15% (5-24%) and 2-year overall survival (OS) was 19% with a 95% CI of 7%-31% (1-year OS: 30% (27-34%)]. Multivariate analysis suggested that extent of surgical resection and initial radiotherapy were independent predictors of PFS and OS. Notably, no chemotherapeutic regimen was associated with improved outcome. CONCLUSIONS: NMC portends a poor prognosis among all squamous cell neoplasms and seems to be frequently unrecognized. The finding that conventional chemotherapy has been inadequate indicates a pressing need for the development of targeted therapeutics. Intensive local therapies such as gross total resection and radiotherapy might be associated with enhanced survival.
Histone deacetylase inhibitor for NUT midline carcinoma
AbstractNUT Midline carcinoma (NMC) is a rare and invariably fatal poorly differentiated carcinoma characterized by chromosomal rearrangement involving the nuclear protein of the testis (NUT) gene. Current approaches do not provide durable response. We report a case of widely metastatic NMC in a 17-year-old female who, following an initial response to combination chemotherapy developed rapid disease progression. Treatment with vorinostat, a histone deacetylase inhibitor (HDACi) resulted in an objective response, yet she died in less than one year from initial diagnosis. This report shows a potentially promising activity of HDACi in the treatment of NMC that needs further exploration.
Journal of Pediatric Hematology/Oncology · 2013 · 27 citations
A Case of NUT Midline Carcinoma With Complete Response to Gemcitabine Following Cisplatin and Docetaxel
AbstractBACKGROUND: NUT midline carcinoma (NMC) is recognized as a very rare tumor that most often occurs around the midline and shows NUT rearrangement. This tumor affects children and younger adults, progresses rapidly, and shows an extremely poor prognosis, even with intensive chemotherapy. Very few reports have described effective treatment for this tumor. METHODS: A 12-year-old girl with NMC was treated using cisplatin (CDDP), docetaxel, gemcitabine, pemetrexed, and vinorelbine. RESULTS: Imaging showed partial response with CDDP and docetaxel, and complete response with gemcitabine. After reexacerbation of the tumor, although partial response was achieved with vinorelbine, the patient died 89 weeks after onset because of reexacerbation. CONCLUSIONS: NMC is a very rare disease with poor prognosis. This study is the first to report response of NMC to gemcitabine and vinorelbine. The findings suggest that combination chemotherapies including CDDP, docetaxel, gemcitabine, and vinorelbine may be a choice in the treatment for NMC.
Journal of Pediatric Hematology/Oncology · 2020 · 13 citations
Metastatic NUT Midline Carcinoma Treated With Aggressive Neoadjuvant Chemotherapy, Radiation, and Resection: A Case Report and Review of the Literature
AbstractNUT midline carcinoma, characterized by the rearrangement of the nuclear protein in testis (NUTM1) gene, is a rare and aggressive subtype of squamous cell carcinoma. This disease is rarely cured and there have been no reports of cure in patients with distant metastatic disease. In fact, patients typically succumb to NUT midline carcinoma within 6 to 12 months from diagnosis. The authors report on a single patient who presented widely metastatic disease who has now been in remission for 37 months after multimodal therapy with compressed cycles of vincristine, cyclophosphamide, and doxorubicin alternating with ifosfamide and etoposide, high-dose radiation, and postchemotherapy resection.
Journal of Cancer Research and Therapeutics · 2023 · 10 citations · open access
Immunotherapy experience in sinonasal NUT midline carcinoma, case report
AbstractNUT midline carcinoma (NMC) is an aggressive malignant neoplasm arising from midline structures. Although it is classified as a rare disease, the pathological nonspecific appearance as undifferentiated/poorly differentiated carcinoma and the difficulty in making the definitive diagnosis are probably the reasons for the underdiagnosis; the disease is thought to be more prevalent. There is no standard treatment for the disease. The disease shows a poor response to chemotherapy and radiotherapy, and patients' survival is poor. We present a case of sinonasal NMC treated with chemotherapy and immunotherapy in first-line, which is the first in the literature. The patient presented with metastatic disease and received cisplatin-fluorouracil-docetaxel-pembrolizumab treatment. The tumor's PD-L1 expression was 10%, evaluated by tumor proportion score. The response to the therapy was poor, and the patient died of disease progression 5.4 months after the diagnosis. The efficacy of immunotherapy in NMC is not known. More reports are needed to draw conclusions.
Journal of Neurological Surgery Part B Skull Base · 2018 · 2 citations · open access
Sinonasal Nuclear Protein Testis Midline Carcinoma: Case Report with a Review of the Literature
AbstractBackground Nuclear protein testis (NUT) midline carcinoma is a rare undifferentiated epithelial malignancy of the upper midline structures. Most often arising in the thorax or head and neck in young patients, NUT carcinoma is highly aggressive and associated with high mortality. Despite treatment, the average survival time is less than 1 year, with overall survival of 19% at 2 years. There is little consensus on the optimal treatment regimen, including the role for surgery. We report two successful cases of sinonasal NUT midline carcinoma treated with upfront surgery followed by adjuvant chemoradiation.
American Journal of Clinical Pathology · 2015 · 0 citations · open access
A Rare Case of Pericardial NUT Midline Carcinoma Without Squamous Differentiation
AbstractNUT midline carcinoma is a rare form of squamous cell carcinoma, defined by a characteristic translocation involving the gene nuclear protein in the testis (NUT). First described in 1991, it is an aggressive tumor and almost universally fatal. The case described is of a 2-year-old girl who presented with an incidentally discovered 7 cm pericardial mass during follow-up of suspected pneumonia. The mass was partially resected due to significant involvement of the myocardium. It was received as multiple specimens consisting of fragmented, soft, pink tissue. Microscopic examination revealed round to ovoid cells in a nested pattern. Nuclei were irregular and surrounded by scant, pale cytoplasm. Focal areas of spindled morphology as well as myxoid change were also noted. No overt squamous differentiation was appreciated. By immunohistochemistry, only rare cells were positive for pancytokeratin AE1/AE3, and CD99 showed focal membranous staining. Nuclear INI positivity was retained. CD45, TdT, S100, desmin, and myogenin were all negative. A t(15;19)(q12-14;q13.3) rearrangement was identified by conventional cytogenetics. Subsequent immunohistochemistry demonstrated diffuse nuclear staining for NUT antibody in a speckled pattern. NUT midline carcinoma is a rare entity, with only 10–15 cases reported annually. Most often diagnosed in children within the head and neck or mediastinum, to our knowledge, this is the first reported case arising from pericardium. Most exhibit focal, often abrupt, squamous differentiation. Only exceptionally is mesenchymal differentiation seen. NUT carcinoma is defined by t(15;19) rearrangement. A speckled pattern of nuclear staining for NUT protein by immunohistochemistry is highly specific for NUT carcinoma. Diagnosis can be confirmed by fluorescent in situ hybridization. Awareness that this entity may present in the pediatric population and mimic primitive round cell sarcomas is critical to accurate diagnosis. Lastly, this case underscores the utility of cytogenetics in the diagnosis of unusual pediatric tumors.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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