DeCure for Hereditary diffuse gastric adenocarcinoma
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for hereditary diffuse gastric adenocarcinoma — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary diffuse gastric adenocarcinoma maps to a 6-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 hereditary diffuse gastric adenocarcinoma 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
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome linked to germline mutations in the CDH1 tumour suppressor gene. Of families meeting clinical criteria for HDGC, only about 25% carry a CDH1 mutation. The syndrome is characterised by high penetrance, early onset, poor tumour differentiation, and a high risk of inheritance. No reliable surveillance technique exists for individuals with HDGC. The only currently recommended risk-reducing intervention is prophylactic total gastrectomy for patients with pathogenic or likely pathogenic CDH1 variants. The physical and psychosocial consequences of complete stomach removal are substantial and require further investigation.
A 2025 case report of a three-generation Chinese family of four individuals illustrates the clinical heterogeneity of HDGC and the considerable dilemmas encountered in its management. The report integrates clinical, pathological, imaging, genetic, and survival outcome data but does not provide specific survival or response numbers. A 2018 review notes that while international standards exist for aetiology, pathology, diagnosis, and treatment, China lacks effective diagnosis, treatment, and genetic screening for HDGC due to inadequate awareness. A 2012 review states that difficult decisions must be made between prophylactic total gastrectomy and lifelong annual surveillance, with no reliable surveillance technique available.
A 2023 narrative review addresses the risks and benefits of prophylactic total gastrectomy for HDGC in the context of other highly penetrant cancer syndromes. It confirms that risk-reducing total gastrectomy is currently recommended for CDH1 mutation carriers but emphasises that the sequelae of complete stomach removal are substantial. No chemoprevention or drug-based intervention is mentioned in any of these abstracts. No drug is named, no response rate or survival benefit from any pharmacological treatment is reported.
What remains missing is any evidence for a drug that could delay or prevent HDGC onset, any reliable non-surgical surveillance method, and any randomised trial comparing gastrectomy to alternative strategies. Patient stratification beyond CDH1 mutation status is not addressed, and no funding for drug-repurposing studies in HDGC is described.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
European Journal of Cancer Prevention · 2023 · 5 citations · open access
Unique challenges of risk-reducing surgery for hereditary diffuse gastric cancer syndrome: a narrative review
AbstractThe common use of genetic testing has reinvigorated discussions surrounding enhanced cancer surveillance, chemoprevention, and preventive surgery strategies due to increasing recognition of pathogenic germline genetic variants. Prophylactic surgery for hereditary cancer syndromes can significantly reduce the risk of developing cancer. Hereditary diffuse gastric cancer (HDGC), characterized by high penetrance and an autosomal dominant inheritance pattern, is causally linked to germline mutations in the CDH1 tumor suppressor gene. Risk-reducing total gastrectomy is currently recommended in patients with pathogenic and likely pathogenic CDH1 variants; however, the physical and psychosocial sequelae of complete stomach removal are substantial and need to be investigated further. In this review, we address the risks and benefits of prophylactic total gastrectomy for HDGC in the context of prophylactic surgery for other highly penetrant cancer syndromes.
Journal of Surgical Case Reports · 2012 · 2 citations · open access
Prevention is better than cure
AbstractThe vast majority of gastric cancers are sporadic. However, 1-3% arise as a result of inherited gastric cancer predisposition syndromes, generally referred to as hereditary diffuse gastric cancer (HDGC). Of those families that fulfill the clinical criteria for HGDC only 25% have a CDH1 germline mutation. No reliable surveillance technique exists for individuals with HDGC. Difficult decisions have therefore to be made by mutation carriers to proceed with prophylactic total gastrectomy, or undergo lifelong annual surveillance. We present a case of the management of a patient with a documented CDH1 mutation and briefly review the available literature.
Frontiers in Oncology · 2025 · 0 citations · open access
Hereditary diffuse gastric cancer: a case report
AbstractHereditary diffuse gastric cancer (HDGC) is an autosomal dominant genetic syndrome characterized by distinct clinical and genetic features. It exhibits low clinical incidence, familial clustering, early onset, insidious progression, and challenges in early diagnosis. In addition, HDGC is marked by poor tumor differentiation, high malignancy, specific gene mutations, frequent occurrence of extra-gastric tumors, and a high risk of inheritance, which poses significant challenges to clinical medicine, medical genetics, and reproductive medicine. In this study, we have reported a case of HDGC in a three-generation Chinese family of four individuals. By integrating clinical, pathological, imaging, genetic mutation, family history, diagnostic and treatment process, and the survival outcome data, it fully demonstrates the clinical heterogeneity of HDGC and the considerable dilemmas encountered in its management. These findings together provide valuable insights into the clinical diagnosis and treatment of related cases, literature research, as well as the management of cancer-related genetic diseases and reproductive health.
Research progress, diagnosis and treatment of hereditary diffuse type of gastric cancer
AbstractHereditary diffuse type of gastric cancer is a common type of hereditary gastric cancer. It has been decades since the disease was discovered. A series of studies has been carried out overseas and there has been a certain degree of standards and consensus on the etiology, pathological features, diagnosis and treatment of this type of gastric cancer. However, the disease lacks effective diagnosis, treatment as well as the genetic screening in China due to inadequate awareness and concern. This review focuses on the recent advances in the hereditary diffuse type of gastric cancer.
Key words:
Hereditary diffuse gastric cancer; Gene mutation; Diagnosis; Treatment; Screening
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.
