DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Tracheal Carcinoma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTracheal Carcinoma maps to a 1-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 tracheal 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
KRas proto-oncogene, GTPase (KRAS) — KRAS 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 gnpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7VVB · 1.7 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER (GNP). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 audit of the Netherlands Cancer Registry found that one-third of cases registered as primary tracheal carcinoma were actually misclassified nontracheal primary tumours involving the trachea. Among 50 confirmed cases reviewed by a multidisciplinary panel and a second reviewer, actual treatment consisted of surgery in 12 (24%), radiotherapy in 29 (58%), endobronchial treatment in 6 (12%), and observation in 3 (6%). Both the panel and the second reviewer identified 16 additional surgical candidates, meaning 28 of 50 patients (56%) met audit criteria for surgical resection but a majority were treated with other modalities. Inter-reviewer disagreement on treatment recommendations occurred in only 4 of 50 cases (8%). The authors concluded that incorrect diagnosis and undertreatment are common in rare airway tumours.
A 1986 review noted that tracheal carcinoma is rare compared with other respiratory tract neoplasms and that, unlike bronchus and lung carcinoma, its incidence has not risen with tobacco consumption. The authors suggested that some mechanism renders the trachea especially resistant to malignant change, but provided no further data on treatment or outcomes.
A 2021 case report described the first documented BRG (SMARCA4)/INI deficient tracheal carcinoma, a new entity introduced in the WHO Classification of Tumors, 5th edition, 2021. The patient was a 60-year-old male with a history of tobacco abuse who presented with shortness of breath and a tracheal mass. Microscopic examination showed a high-grade, poorly differentiated carcinoma with tumour necrosis, high mitotic counts, and marked nuclear pleomorphism. Immunohistochemistry showed negative staining for BRG (SMARCA4) expression while INI 1 was intact. The authors stated that this entity is very aggressive with a poor prognosis and that targeted therapy or clinical trials may become available as additional cases are diagnosed.
What is still missing is prospective data on treatment outcomes for any histological subtype of tracheal carcinoma, including the newly described BRG/INI deficient variant. No randomised trials or systematic comparisons of surgery, radiotherapy, or systemic therapy exist for this disease. The 2008 audit highlights diagnostic misclassification and underuse of surgery, but does not report survival or response rates. Funding for multicentre registries, standardised pathological review, and trials that stratify by histology and resectability status is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Surgical Oncology · 2008 · 52 citations · open access
Undertreatment of Tracheal Carcinoma: Multidisciplinary Audit of Epidemiologic Data
AbstractNational epidemiologic data were examined to determine the eligibility for curative therapy in tracheal carcinoma. An expert audit of primary tracheal carcinomas registered from 2000 to 2005 with the Netherlands Cancer Registry (NCR) included blinded patient data and radiographic review to assess diagnosis and resectability. Actual treatment was compared with the opinions of a multidisciplinary panel (Radboud panel) and a second reviewer. Of 101 NCR-registered primary tracheal carcinomas, the Radboud panel diagnosis was metastatic disease or local extension of adjacent tumors in 34. Seventeen cases were excluded for missing data. In 50 cases confirmed by panel and a second reviewer, actual treatment consisted of surgery in 12 (24%), radiotherapy in 29 (58%), endobronchial treatment in 6 (12%), and observation in 3 (6%). Both panel and second reviewer identified 16 additional surgical candidates, a total of 28 (56%) of 50. Treatment recommendations of panel and second reviewer disagreed in four cases (8%). One-third of NCR-registered primary tracheal carcinomas were misclassified nontracheal primary tumors involving the trachea. A majority of cases meeting audit criteria for diagnosis and surgical resection was treated with other modalities. Interreviewer disagreement was small. The audit of a national cancer registry suggests that incorrect diagnosis and undertreatment are common in rare airway tumors.
The Journal of Laryngology & Otology · 1986 · 2 citations
Tracheal carcinoma following short term tracheostomy in childhood
AbstractCarcinoma of the trachea is rare in comparison to other neoplasms of the respiratory tract. Cigarette smoking has been implicated in its aetiology, but unlike carcinoma of the bronchus and lung, the incidence of tracheal carcinoma has not risen with tobacco consumption (Hajdu et al., 1970; Ranke et al., 1962). It seems, then, that there is some mechanism or mechanisms which render the trachea especially resistant to malignant change.
American Journal of Clinical Pathology · 2021 · 0 citations · open access
The first case of BRG (SMARCA4)/INI Deficient Tracheal Carcinoma: A Case Report and Review of the Literature
AbstractAbstract Introduction/Objective Primary tumors of the trachea are rare, they account for less than 0.1% of tumors in humans. In adults, 90% of primary tracheal tumors are malignant, with squamous cell carcinoma and adenoid cystic carcinoma accounting for two-thirds, with other forms occurring less frequently. The BRG (SMARCA4)/INI deficient tumor is a relatively new defined entity which is recently introduced in the WHO Classification of Tumors, 5th edition, 2021. The gene SMARCA4 is located at 19p13. Loss of SMARCA4 has been reported in several aggressive tumors with high- grade undifferentiated rhabdoid morphology but has not been reported in the trachea. Hence, we report the first case of BRG (SMARCA4)/ INI deficient tracheal carcinoma. Methods/Case Report We present a 60-year-old male with a history of tobacco abuse, shortness of breath, and a tracheal mass on chest imaging. Bronchoscopy was performed and showed a fleshy friable lesion at the anterior trachea with evidence of blood dripping into the distal airways. Results (if a Case Study enter NA) Microscopic examination showed a high grade, poorly differentiated carcinoma with tumor necrosis, high mitotic counts, and marked nuclear pleomorphism. Immunohistochemical stains were performed. The tumor cells were strongly and diffusely positive for CK-7 and weakly positive for synaptophysin, negative for pan-cytokeratin, TTF-1, CK-20, p40, CK5/6, and chromogranin. Then BRG (SMARCA4) and INI 1 (BAR47) were performed and showed negative staining on BRG expression, while INI 1 is intact (nuclear expression). These features are consistent with BRG (SMARCA4)/ INI deficient carcinoma. Conclusion BRG (SMARCA4)/ INI deficient carcinoma is a new entity in the trachea, which is very aggressive with a poor prognosis. Targeted therapy or clinical trials may be available as additional cases are diagnosed in the future.
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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