DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for gastric cardia 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 moduleGastric cardia 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 gastric cardia 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.
What the evidence adds up to
Gastric cardia carcinoma is a distinct subtype of gastric cancer. A 2005 study of 165 cardia carcinoma patients (74 true cardia, 91 subcardia) compared with 564 noncardia carcinoma patients found that cardia tumours were more often poorly differentiated (P = 0.012), diffuse type by Lauren classification (P = 0.049), and at an advanced pathologic TNM stage (P < 0.001). Loss of the tumour suppressor genes p16 (P = 0.038) and smad4 (P < 0.001) was more frequent in cardia carcinoma, as was overexpression of carcinoembryonic antigen and CD44 (P < 0.05). Expression of MUC1 (P = 0.008) and MUC5AC (P = 0.006) was less frequent. Epstein-Barr virus infection was more common in cardia carcinoma (P < 0.001). Tumour location in the cardia was an independent poor prognostic factor in multivariate analysis.
A French registry study covering 1984 to 2003 reported that the standardised incidence of distal gastric carcinomas fell from 10.74 to 5.68 per 100,000 inhabitants per year (P < 0.001), while the incidence of cardia carcinomas did not increase significantly (0.83 to 1.25 per 100,000). The frequency of macroscopically infiltrating tumours doubled (P < 0.001) and linitis plastica rose from 9% to 16.2% (P < 0.001). Overall survival improved only for patients with metastatic carcinomas of either location (P < 0.001) and for those with advanced distal stomach tumours receiving therapy (P < 0.001). The authors concluded that prognosis remains dismal.
A 1987 paper on treatment strategies for cardia carcinoma noted no clear operative consensus. It recommended abdominal gastrectomy for fundus tumours involving the cardia without oesophageal infiltration, abdominothoracal gastrectomy for typical cardia carcinoma in younger patients, and abdominothoracal proximal resection for high-risk patients. Barrett's carcinoma was to be treated like oesophageal cancer. A 2015 commentary on genetic variants reported that the PLCE1 rs2274223 variant was significantly associated with cardia cancer risk but not noncardia cancer risk, with high credibility, supporting the view that cardia carcinoma shares risk factors with oesophageal cancer. A 2012 review stated that gastric cancer incidence and mortality in the USA had remained largely unchanged since 2005, with approximately 10,540 deaths per year.
What is still missing is a prospective trial that stratifies cardia carcinoma separately from other gastric cancers, given its distinct biology and poor prognosis. No drug is mentioned in these abstracts, so no repurposing candidate can be identified from this evidence. The field lacks a standardised molecular classification that could guide targeted therapy for this subgroup, and funding for such stratified trials remains insufficient.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 2005 · 71 citations · open access
Clinicopathologic and protein expression differences between cardia carcinoma and noncardia carcinoma of the stomach
AbstractBACKGROUND: Although the incidence of adenocarcinoma of the stomach has decreased over the past several decades, gastric cardia carcinoma has increased over the same period. METHODS: The clinicopathologic characteristics and immunohistochemical staining results of 21 proteins were investigated in 165 patients with cardia carcinoma, including 74 patients with true cardia carcinoma and 91 patients with subcardia carcinoma, and the results were compared with the results from 564 patients with noncardia carcinoma. RESULTS: In the clinicopathologic analysis, patients who had cardia carcinoma tended to have tumors with poorly differentiated histology according to the World Health Organization classification system (P = 0.012), diffuse type according to the Lauren classification system (P = 0.049), and advanced pathologic TNM stage (P < 0.001). On immunohistochemical staining, loss of the p16 (P = 0.038) and smad4 (P < 0.001) tumor suppressor genes was more frequent in cardia carcinoma than in noncardia carcinoma. Carcinoembryonic antigen and CD44 overexpression were more frequent in patients with cardia carcinoma (P < 0.05). Conversely, patients who had cardia carcinoma exhibited less frequent expression of MUC1 (P = 0.008) and MUC5AC (P = 0.006) compared with patients who had noncardia carcinoma. Epstein-Barr virus infection was more common in patients with cardia carcinoma (P < 0.001). In the survival analysis, the patients with cardia carcinoma had a poorer prognosis. In the multivariate analysis, tumor location in the cardia was confirmed as an independent, poor prognostic factor in patients with gastric carcinoma. CONCLUSION: Cardia carcinoma and noncardia carcinoma differed in their clinicopathologic characteristics and in their alterations of gene expression, as evaluated by immunohistochemistry. The current results support the hypothesis that cardia carcinoma forms a specific category of gastric carcinoma that is distinct from noncardia carcinoma.
Scandinavian Journal of Gastroenterology · 1987 · 13 citations
Carcinoma of the Gastric Cardia: Factors Influencing the Choice of Therapy and the Outcome of Different Treatment Modalities
AbstractCarcinoma of the gastric cardia is a cancer found with increasing frequency. Nevertheless, there are no clear strategies for the operative treatment of this cancer. In accordance with the long-term complications and postoperative quality of life we recommend abdominal gastrectomy for carcinomas of the gastric fundus involving the cardia without infiltration of the esophagus. Barett's carcinoma should be treated like esophageal cancer. The typical carcinoma of the cardia is best treated by abdominothoracal gastrectomy in younger patients, whereas in high-risk patients we prefer the abdominothoracal proximal resection.
Genetic variant <i>PLCE1</i> rs2274223 and gastric cancer: more to be explored?
AbstractWe read with great interest the comprehensive study by Mocellin and colleagues1 who developed a quantitative summary of candidate genetic variants for gastric cancer susceptibility. Based on different tumour sites, the authors conducted a subgroup analysis for cardia cancer (CC) and non-cardia cancer (NCC). It is well established that CC has distinctive characteristics compared with NCC, but shares some common risk factors and pathogenesis with oesophageal cancer (OSC). In addition, there are some different genetic factors such as genetic variants between patients with CC and NCC. There is an argument that CC, located at oesophago-gastric junction, belongs to oesophageal more than gastric cancer.
According to the results of subgroup analysis, Mocellin and colleagues1 found several variants showing different results with CC and NCC risk. However, only PLCE1 rs2274223 was reported to be significantly associated with CC but not NCC risk with high credibility …
European Journal of Gastroenterology & Hepatology · 2010 · 11 citations
Trends in incidence, management, and survival of gastric and cardia carcinomas in the area of Finistere (France) between 1984 and 2003
AbstractOBJECTIVE: The aim of this study was to evaluate trends in incidence and prognosis of gastric and cardia carcinomas in the area of Finistère (France) between 1984 and 2003. METHODS: The Digestive Tumor Registry of Finistère recorded all new cases of gastric and cardia carcinomas from January 1, 1984 to December 31, 2003. Raw incidence data were standardized using the direct method based on the reference world population. The data and survival rates were studied in univariate and multivariate analyses. RESULTS: Between 1984-1988 and 1999-2003 the standardized incidence of distal gastric carcinomas decreased (10.74 ± 0.39-5.68 ± 0.27/year/100 000 inhabitants, P < 0.001). There was no significant increase in the incidence of cardia carcinomas (0.83 ± 0.11-1.25 ± 0.14/year/100 000 inhabitants). The frequency of macroscopically infiltrating tumors doubled (P < 0.001) and linitis plastica increased from 9 to 16.2% (P < 0.001). Overall survival rates increased only for patients with metastatic carcinomas of both locations (P < 0.001) and with advanced tumors of distal stomach (P < 0.001) receiving therapy. CONCLUSION: This study showed a significant decrease over time in the incidence of distal gastric carcinomas but no significant increase in the incidence of cardia carcinomas. Despite improvement in the management of patients, prognosis remains dismal, probably because of an increased incidence of poor prognosis of histological and anatomical types.
Gastric cancer: past accomplishments, present approaches and future aspirations
AbstractSUMMARY The incidence and mortality of gastric cancer has remained largely unchanged since 2005 and approximately 10,540 patients succumb to the disease each year in the USA. The subject of gastric carcinoma is an area of active research by many groups around the world who are investigating the biology of the disease, as well as newer and more efficacious methods of detection and treatment. This review will provide an introduction to gastric cancer epidemiology and biology, and will serve as an overview of the evolution of the treatment of gastric cancer with a focus on present day management, including surgery, chemotherapy, radiation therapy and novel therapeutic modalities.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
