DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Gastric Papillary Adenocarcinoma — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGastric Papillary Adenocarcinoma maps to a 3-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 papillary 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
tumor protein p53 (TP53) — TP53 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9R2Q · 3.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Gastric adenocarcinoma remains a leading cause of cancer death worldwide, and despite improvements in chemotherapy and surgical technique over recent decades, overall survival is still low. The disease is molecularly heterogeneous, with distinct subtypes defined by the TCGA and ACRG consortia, and a growing list of genomic alterations are being investigated as potential treatment targets. However, these remain largely at the stage of preclinical or early clinical exploration; no single targeted agent has yet changed the standard of care for the general gastric adenocarcinoma population.
In a retrospective study of 56 patients with recurrent or metastatic gastric adenocarcinoma, the FOLFOX regimen (oxaliplatin, leucovorin, fluorouracil) produced a response rate of 43.3% (one complete response, 12 partial responses) and a median time to progression of 4 months, while the FOLFIRI regimen (irinotecan, leucovorin, fluorouracil) produced a response rate of 46.2% (two complete responses, 10 partial responses) and a median time to progression of 4.5 months. Overall survival was not significantly different between the groups: 8.3 months for FOLFOX and 9.7 months for FOLFIRI. Grade 3/4 neutropenia occurred in 4 patients on FOLFOX and 9 on FOLFIRI. The authors concluded both combinations can be used safely and effectively, but the sample is small and the study is retrospective.
Linitis plastica, a diffusely infiltrative form of gastric adenocarcinoma, carries a particularly poor prognosis. In a multi-institutional analysis of 869 resected patients, 58 had linitis plastica. These patients presented at more advanced stages (90% stage III/IV versus 44% of non-LP patients), more often required total gastrectomy (88% versus 57%), and had higher rates of positive margins (33% versus 7%). Median overall survival for LP patients was 11.6 months versus 37.8 months for non-LP patients. However, among patients who achieved an optimal resection (R0 with D2 lymphadenectomy), median survival for stage III LP patients was 26.8 months, nearly identical to the 25.3 months seen in stage III non-LP patients. The poor prognosis of linitis plastica appears driven by late diagnosis rather than an inherently more aggressive biology after complete resection.
What is still missing are prospective trials that stratify patients by molecular subtype, validated biomarkers to guide the use of emerging targeted agents, and adequately powered studies to determine whether the promising survival seen in optimally resected linitis plastica patients can be replicated in a broader, unselected surgical population. The field lacks the financial and organisational commitment needed to move from retrospective observations and molecular catalogues to practice-changing randomised evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancers · 2021 · 41 citations · open access
Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View
AbstractGastric cancer is a leading cause of cancer death worldwide. Systemic treatment comprising chemotherapy and targeted therapy is the standard of care in advanced/metastatic gastric cancer. Comprehensive molecular characterization of gastric adenocarcinomas by the TCGA Consortium and ACRG has resulted in the definition of distinct molecular subtypes. These efforts have in parallel built a basis for the development of novel molecularly stratified treatment approaches. Based on this molecular characterization, an increasing number of specific genomic alterations can potentially serve as treatment targets. Consequently, the development of promising compounds is ongoing. In this review, key molecular alterations in gastric and gastroesophageal junction cancers will be addressed. Finally, the current status of the translation of targeted therapy towards clinical applications will be reviewed.
AbstractGastric adenocarcinoma is a complex disease that requires a thorough multidisciplinary approach for appropriate management. Management strategies vary in different regions of the world and have changed over time. In spite of improvements in chemotherapy and surgical techniques and an improvement in outcomes over the last several decades, overall survival remains low. The best outcomes are likely related to early detection, preoperative reduction of tumor burden with immunochemotherapy, consistent surgical technique for resection, and postoperative eradication of tumor cells. We aim to describe the management for gastric cancer, from the specifics of staging and imaging workup to the tenets of surgical resection and reconstruction as well as the adjuvant treatment strategies in this broad review of gastric cancer management.
Journal of Surgical Oncology · 2022 · 11 citations · open access
Molecular pathogenesis and emerging targets of gastric adenocarcinoma
AbstractGastric adenocarcinoma (GC) is a devastating disease and is the third leading cause of cancer deaths worldwide. This heterogeneous disease has several different classification systems that consider histological appearance and genomic alterations. Understanding the etiology of GC, including infection, hereditary conditions, and environmental factors, is of particular importance and is discussed in this review. To improve survival in GC, we also must improve our therapeutic strategies. Here, we discuss new targets that warrant further exploration.
Korean Journal of Gastroenterology · 2010 · 5 citations · open access
Oxaliplatin and Leucovorin Plus Fluorouracil Versus Irinotecan and Leucovorin Plus Fluorouracil Combination Chemotherapy as a First-line Treatment in Patients with Metastatic or Recurred Gastric Adenocarcinoma
AbstractBACKGROUND/AIMS: We performed retrospective study in order to compare oxaliplatin, leucovorin, and fluorouracil (FOLFOX) versus irinotecan, leucovorin, and fluorouracil (FOLFIRI) in recurred or metastatic gastric adenocarcinoma. METHODS: We investigated 56 patients who were diagnosed with recurred or metastatic gastric adenocarcinoma in a single center during march, 2003 to march, 2008. The patients received either FOLFOX or FOLFIRI chemotherapy. RESULTS: There were no significant difference between the Oxaliplatin group (30 patients) and Irinotecan group (26 patients) in sex, age, and ECOG performance (p<0.05). Oxaliplatin group showed 1 case of CR (3.3%) and 12 cases of PR (40%), making the response rate 43.3%. Irinotecan group showed CR in 2 cases (7.7%) and PR in 10 cases (38.5%), making the response rate 46.2%. The median value of time to progression was 4 months in the oxlaplatin group and 4.5 months in the irinotecan group. The overall survival showed no significant difference (p=0.784), with the irinotecan group (9.7 months) being slightly longer than the Oxaliplatin group (8.3 months). Grade 3/4 neutropenia occurred similarly in both groups (4 cases in the oxalplatin group, 9 in the irinotecan group). CONCLUSIONS: Both combination treatment can be used safely and effectively in recurred or metastatic gastric adenocarcinoma.
Is linitis plastica a contraindication for surgical resection? A 7-institution study of the U.S. Gastric Cancer Collaborative.
Abstract118 Background: Linitis plastica (LP) describes a diffusively infiltrative gastric adenocarcinoma that portends poor prognosis. Current treatment guidelines do not differentiate between LP and non-LP cancers and it is not known if the same staging system should be applied to both situations. Methods: Using the multi-institutional U.S. Gastric Cancer Collaborative database, 869 patients with gastric adenocarcinoma who underwent resection between 2000-2012 were identified. Clinicopathologic, perioperative and survival outcomes of the 58 patients with LP were compared to the 811 patients without LP. Results: Advanced disease (stage III/IV) at presentation was more common in patients with LP compared to non-LP patients (90 vs 44%, p<0.01). Despite the fact that most LP patients underwent total gastrectomy (88% vs 57%, p<0.01), positive margins were more common in LP patients (33 vs 7%, p<0.01). There was no difference in perioperative complications (48 vs 43%, p=0.45) or mortality (7 vs 3%, p=0.12) between LP and non-LP patients. While survival correlated with stage in non-LP patients, there was no difference in median overall survival (OS) of LP patients based on stage (I/II, 17.3 mos; III, 10.6 mos; IV, 12.0 mos; p=0.46). Median OS was significantly worse in patients with LP (11.6 vs 37.8 months, p<0.01) when margin status and extent of lymphadenectomy were not factored in the analysis. However, when analyzing only patients with optimal resections (R0, D2 lymphadenectomy), the median OS for stage III LP (n=22) and non-LP (n=185) patients was nearly identical (26.8 vs 25.3 mos, p=0.69). There were no independent prognostic factors identified to predict survival in LP patients undergoing curative resection. Conclusions: The poor prognosis of LP gastric cancer is due primarily to its advanced stage at diagnosis. However, LP patients who undergo optimal resections can expect similar long term survival compared to optimally resected non-LP patients with advanced stage disease. Patient selection and multidisciplinary management are paramount when considering surgical resection in patients with gastric LP.
International Journal of Surgery · 2017 · 0 citations
Advances in molecular targeted therapy of adenocarcinoma of the esophagogastric junction
AbstractAdenocarcinoma of the esophagogastric junction is a special type of tumor, not only in the special location, but also in the biological characteristics and clinical manifestations are unique. Surgery is the main treatment, but surgery alone sometimes result in poor prognosis. as a new direction of cancer treatment, Molecular targeting therapy is playing an increasingly important role. Some molecular targets such as vascular endothelial growth factor, hepatocyte growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor 2, human epidermal growth factor receptor-2 in the treatment of esophageal gastric adenocarcinoma show a broad prospect. This review summarizes the current status and progress of molecular targeted therapy of adenocarcinoma of esophagogastric junction.
Key words:
Adenocarcinoma of the esophagogastric junction; Molecular targeted therapy; Research; Review
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.
