DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for ethmoid sinus squamous cell carcinoma — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEthmoid sinus squamous cell carcinoma maps to a 7-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 ethmoid sinus squamous cell 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
notch receptor 2 (NOTCH2) — NOTCH2 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 bgcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5MWB · 1.86 Å · ligand beta-D-glucopyranose (BGC). Experimental structure, not a prediction.
What the evidence adds up to
The available literature on ethmoid sinus squamous cell carcinoma is limited and mostly retrospective, covering small patient series over many decades. A 1989 series from the Cleveland Clinic reported that only 6 of 54 squamous cell carcinomas of the paranasal sinuses arose from the ethmoid sinus; 1 of those 6 patients had a local recurrence, and 3 of the 6 were cured. In a 2009 retrospective study of 34 patients with ethmoid sinus carcinoma of all histological types, squamous cell carcinoma was the most frequent type (44 per cent). The five-year actuarial observed survival rate for all patients in that study was 44 per cent. Eleven patients had T4b disease, and 2 patients (6 per cent) had nodal metastasis at diagnosis. The authors recommended combined surgery and post-operative radiotherapy for local control but did not recommend prophylactic neck treatment.
The other abstracts address adenocarcinoma of the ethmoid sinus, not squamous cell carcinoma, and their results cannot be directly applied. A 2001 Dutch series of 62 patients with ethmoidal adenocarcinoma treated with surgical debulking and topical fluorouracil reported adjusted disease-free survival of 96 per cent at 2 years, 87 per cent at 5 years, and 74 per cent at 10 years. However, that regimen has not been tested in squamous cell carcinoma. A 1999 study found H-ras point mutations in 5 of 31 ethmoid sinus adenocarcinomas (16 per cent); those mutations were associated with shorter tumour-free survival (P = 0.04) and overall survival (P = 0.008), but again this finding is specific to adenocarcinoma and not squamous histology.
What is still missing is any prospective trial dedicated to ethmoid sinus squamous cell carcinoma specifically. The available data are from small, single-institution retrospective reviews spanning decades, with no standardised staging or treatment protocols. No drug has been tested in a controlled fashion for this disease. A dedicated trial would require multi-centre collaboration to recruit enough patients, given the rarity of the tumour, and would need to stratify by histological subtype, T classification, and molecular markers such as H-ras mutation status.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Archives of Otolaryngology - Head and Neck Surgery · 2001 · 103 citations · open access
Adenocarcinoma of the Ethmoidal Sinus Complex
AbstractOBJECTIVES: To report our experience with the management of adenocarcinoma of the ethmoidal sinuses using a regimen of surgical debulking and topical chemotherapy, to report long-term survival, and to compare our results with recently published series of patients undergoing craniofacial resection. DESIGN: Review of prospectively collected data. SETTING: Tertiary cancer center. PATIENTS: Seventy consecutive patients with ethmoidal adenocarcinoma referred to the Department of Head and Neck Surgery, University Hospital of Rotterdam, Rotterdam, the Netherlands, between January 1976 and December 1997. Sixty-two patients were eligible for primary treatment. INTERVENTIONS: Surgical debulking via an extended anterior maxillary antrostomy followed by a combination of repeated topical chemotherapy (fluorouracil) and necrotomy. Additionally 8 patients (13%) required radiotherapy for local recurrence; 1 patient required surgery for regional lymph node metastases. MAIN OUTCOME MEASURES: Survival measured by the Kaplan-Meier method. Clinical complications related to the therapy. RESULTS: There were no perioperative deaths. Complications did occur, such as temporary periorbital swelling (25 patients [40%]) and temporary cerebrospinal fluid leakage (5 patients [8%]). One patient (1.6%) developed meningitis. Adjusted disease-free survival at 2, 5, and 10 years is 96%, 87%, and 74%, respectively. CONCLUSION: Our 23-year experience with a combination of surgical debulking and repeated topical chemotherapy for patients with adenocarcinoma of the ethmoidal sinuses leads us to believe that it represents the current treatment of choice for these patients for long-term disease-free survival.
Squamous cell carcinoma of the paranasal sinuses: The cleveland clinic experience 1977–1986
AbstractFifty-four of 103 malignancies of the paranasal sinuses treated at the Cleveland Clinic Foundation between 1977 and 1986 were squamous cell carcinomas. Six arose from the ethmoid sinus and 48 from the maxillary sinus. Of the maxillary sinus patients, 11 presented with T1 or T2 lesions, 20 with T3, 16 with T4, and 7 of these had nodal disease. Treatment was surgery and/or radiation therapy. There was local recurrence in 25 of 48 maxillary sinus patients and in 1 of 6 ethmoid patients. Overall 5-year survival was 38.2% in the maxillary sinus group: T1, 100.0%; T2, 85.7%; T3, 31.8%; and T4, 6.7%. Three of six patients with ethmoid tumors were cured. There was a statistical trend for better prognosis in those patients presenting with ethmoid primaries, with early lesions, treated with both radiation and surgery, and with history of inverting papilloma. There were complications of treatment in 10 patients, four of which resulted in death. Local control was the major problem for these patients; therefore, early detection and aggressive local treatment are desirable.
ras Gene mutations in ethmoid sinus adenocarcinoma
AbstractBACKGROUND: The presence of mutations of the 3 ras proto-oncogenes in 31 cases of ethmoid sinus adenocarcinoma, an uncommon tumor type epidemiologically related to professional exposure to wood dust, was studied. METHODS: The authors studied 31 patients with ethmoid sinus adenocarcinoma. The polymerase chain reaction was used to amplify ras specific sequences of DNA isolated from paraffin embedded tumor samples. ras point mutations were subsequently detected with mutation specific oligonucleotide probes. RESULTS: H-ras was found to be mutated in 5 cases (16%). It is noteworthy that all of these mutations were identical and consisted of a G-for-T transversion at the second base of codon 12. H-ras mutations were related to a worse prognosis, with shorter tumor free survival (P = 0.04) and overall survival (P = 0.008). T classification was a significant clinical factor related to survival (P = 0.01 for disease free survival and P = 0.006 for overall survival). The prognostic value of H-ras mutation was consistent after adjustment for T classification. H-ras mutations showed no association with patients' previous exposure to wood dust. K-ras was found to be transformed in a single case; this was the only patient in the series to develop lymph node metastases. In this case, both the nasal tumor and the lymph nodes showed the GAT-for-GGT mutation at codon 12 of K-ras. No activation of the N-ras gene was detected. CONCLUSIONS: The presence of H-ras point mutations defines a subgroup of patients with ethmoid sinus adenocarcinomas for whom the prognosis is very poor. The finding that all of these mutations are identical emphasizes the peculiarity of this type of tumor.
Ethmoid sinus disease: CT evaluation in 400 cases. Part III. Craniofacial resection.
AbstractOf 400 patients with ethmoid sinus disease, 18 had undergone craniofacial resection. This operation is an aggressive surgical procedure directed at total en bloc extirpation of tumors that extend through the floor of the anterior cranial fossa. Recent advances in surgical technique have made it the procedure of choice for sinonasal tumors that extend through the cribriform plate, fovea ethmoidalis, and orbital roof. Specifically, this operation has had excellent results in patients with esthesioneuroblastomas. Radiologists must be aware of the possible pitfalls in interpreting the postoperative computed tomographic scans and the findings that suggest tumor recurrence.
The Journal of Laryngology & Otology · 2009 · 12 citations
Treatment results for ethmoid sinus carcinoma
AbstractOBJECTIVE: The aim of this study was to describe the results of treatment in patients with ethmoid sinus carcinoma. MATERIALS AND METHOD: We performed a retrospective study of 34 patients with carcinoma of the ethmoid sinus, and collected the following data: age, sex, employment, tobacco and alcohol consumption, tumour-node-metastasis stage, treatment, and survival. RESULTS: The mean patient age was 64 years. Seventy-six per cent of patients were men and 24 per cent women. Squamous cell carcinoma was the most frequent histological tumour type (44 per cent). Eleven patients were classified as T(2), six as T(3), six as T(4a) and 11 as T(4b). Two patients (6 per cent) had nodal metastasis at the time of diagnosis. The anterior skull base was involved in 17 patients (50 per cent) and the anterior orbital contents were affected in seven patients (21 per cent). The five-year actuarial observed survival rate for all patients was 44 per cent. CONCLUSIONS: Combined treatment with surgery and post-operative radiotherapy permitted good local control in patients with ethmoid sinus carcinoma. We do not recommend prophylactic neck treatment for ethmoid sinus carcinoma.
AbstractThe ethmoid sinus is a collection of approximately nine air cells situated between the upper limit of the nasal fossa and the orbit and closely related to the posterio superior aspect of the maxillary antrum. Cancer in any of these regions may spread rapidly to the adjacent areas, especially as the early disease is frequently asymptomatic. Cancer involving the ethmoid sinus alone is therefore a rare entity, but is more usually part of an uncommon regional disease. A series of 715 tumors of the upper jaw collected by Lederman et al<sup>22</sup>over a period of 35 years included 176 cases of ethmoid cancer, ie, 25%. The basement membrane lining the sinus easily undergoes squamous metaplasia, and approximately 50% of the tumors are squamous cell carcinoma of varying degrees of differentiation, the majority of which are poorly differentiated. The remaining lesions include adenocarcinoma, lymphoma, Ringertz tumor, sarcoma, melanoma, and the
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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