DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for gastric cancer — screening already-approved drugs against its 58-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleGastric cancer maps to a 58-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
approvedDocetaxelApproved drugapprovedEribulinApproved drug
Structures already discussed alongside gastric cancer in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Tubulin-Eribulin complex — Eribulin has a real, experimentally solved structure in complex with this target (PDB 5JH7, 2.25 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 6k9drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5JH7 · 2.25 Å · ligand Eribulin (6K9). Experimental structure, not a prediction.
What the evidence adds up to
A 2010 trial assigned 70 patients with locally-advanced resectable gastric cancer to four cycles of TCF (docetaxel, cisplatin, fluorouracil) either before or after gastrectomy. After preoperative TCF, 94% of patients underwent resection, 85% of which were R0. Pathological complete response occurred in 4 patients (11.7%) and partial response in 18 (55%). No surgical mortality was observed; morbidity was 28.5%, similar to the immediate surgery arm. Serious chemotherapy adverse events tended to be more frequent in the postoperative arm (23% vs 11%, P = 0.07), with one death in each arm. A 2018 review notes that docetaxel alone or in combination can prolong overall response rate and median overall survival in advanced gastric cancer, but the incidence of toxicities is high, there is no uniform dosage standard, and its efficacy is not definite.
A 2018 preclinical study examined low-dose eribulin mesylate, a microtubule dynamics inhibitor approved for advanced breast cancer, in gastric cancer models. In vitro, eribulin at concentrations as low as 0.5 nM for MKN-45 cells and 0.1 nM for human peritoneal mesothelial cells suppressed proliferation and epithelial–mesenchymal transition changes induced by cancer–stromal interaction, partly through downregulation of TGF-β/Smad signalling. In a mouse xenograft model using cocultured cells, eribulin at 0.1 mg/kg suppressed tumour progression (P = 0.02), and at 0.05 mg/kg inhibited fibrosis (P = 0.008). Combining 0.05 mg/kg eribulin with 5-fluorouracil produced synergistic antitumour effects (P = 0.006). These findings are limited to animal and cell models.
A 2008 review describes catumaxomab, a trifunctional antibody targeting EpCAM and CD3, noting that intraperitoneal administration in patients with malignant ascites due to epithelial cancer significantly increased puncture-free survival. The review calls catumaxomab a promising approach in gastric cancer but provides no specific survival or response data from gastric cancer trials. A 2011 review states that for unresectable or metastatic gastric cancer, no significant breakthrough in survival has been achieved with chemotherapy, and recent trials have focused on targeted therapies. A 2022 review on drug repurposing in gastric cancer lists various repurposed drugs but provides no quantitative efficacy data. A 2022 case report reiterates that outcomes in advanced disease remain poor and therapy is rarely curative.
What is still missing are large, randomised controlled trials of repurposed drugs in defined gastric cancer subtypes, standardised dosing regimens for agents such as docetaxel, and validated biomarkers to identify patients most likely to benefit from anti-fibrotic or immunomodulatory approaches. Funding for such trials and for preclinical work that accounts for tumour heterogeneity 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.
PubMed · 2010 · 89 citations · open access
Surgical outcome after docetaxel-based neoadjuvant chemotherapy in locally-advanced gastric cancer.
AbstractAIM: To investigate feasibility, morbidity and surgical mortality of a docetaxel-based chemotherapy regimen randomly administered before or after gastrectomy in patients suffering from locally-advanced resectable gastric cancer. METHODS: Patients suffering from locally-advanced (T3-4 any N M0 or any T N1-3 M0) gastric carcinoma, staged with endoscopic ultrasound, bone scan, computed tomography, and laparoscopy, were assigned to receive four 21 d/cycles of TCF (docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, and fluorouracil 300 mg/m(2) per day for days 1-14), either before (Arm A) or after (Arm B) gastrectomy. Operative morbidity, overall mortality, and severe adverse events were compared by intention-to-treat analysis. RESULTS: From November 1999 to November 2005, 70 patients were treated. After preoperative TCF (Arm A), thirty-two (94%) resections were performed, 85% of which were R0. Pathological response was complete in 4 patients (11.7%), and partial in 18 (55%). No surgical mortality and 28.5% morbidity rate were observed, similar to those of immediate surgery arm (P = 0.86). Serious chemotherapy adverse events tended to be more frequent in arm B (23% vs 11%, P = 0.07), with a single death per arm. CONCLUSION: Surgery following docetaxel-based chemotherapy was safe and with similar morbidity to immediate surgery in patients with locally-advanced resectable gastric carcinoma.
World Journal of Gastrointestinal Surgery · 2014 · 41 citations · open access
Multimodal treatment of gastric cancer
AbstractGastric cancer is the second leading cause of death from malignant disease worldwide. Although complete surgical resection remains the only curative modality for early stage gastric cancer, surgery alone only provides long-term survival in 20% of patients with advanced-stage disease. To improve current results, it is necessary to consider multimodality treatment, including chemotherapy, radiotherapy and surgery. Recent clinical trials have shown survival benefit of combining different neoadjuvant or adjuvant protocols compared with surgery with curative intent. Furthermore, the implementation of chemotherapy with novel targeted agents could play an important role in the multimodal management of advanced gastric cancer. In this paper, we focus on a multidisciplinary approach in the treatment of gastric cancer and discuss future strategies to improve the outcome for these patients.
AbstractGastric cancer (GC) is one of the major causes of death worldwide, ranking as the fifth most incident cancer in 2020 and the fourth leading cause of cancer mortality. The majority of GC patients are in an advanced stage at the time of diagnosis, presenting a poor prognosis and outcome. Current GC treatment approaches involve endoscopic detection, gastrectomy and chemotherapy or chemoradiotherapy in an adjuvant or neoadjuvant setting. Drug development approaches demand extreme effort to identify molecular mechanisms of action of new drug candidates. Drug repurposing is based on the research of new therapeutic indications of drugs approved for other pathologies. In this review, we explore GC and the different drugs repurposed for this disease.
Cancer Management and Research · 2018 · 16 citations · open access
Low-dose eribulin mesylate exerts antitumor effects in gastric cancer by inhibiting fibrosis via the suppression of epithelial–mesenchymal transition and acts synergistically with 5-fluorouracil
AbstractBackground: Characterized by aggressive proliferation, extensive stromal fibrosis, and resulting drug resistance, peritoneal dissemination in gastric cancer remains associated with poor prognosis. Interaction between cancer and stromal cells accelerates tumor progression via epithelial–mesenchymal transition (EMT), which is one of the major causes of tissue fibrosis, and human peritoneal mesothelial cells (HPMCs) play important roles as cancer stroma in peritoneal dissemination. Transforming growth factor-β (TGF-β) has a pivotal function in the progression of EMT, and Smad proteins play an important role in the TGF-β signaling pathway. Eribulin mesylate (eribulin), a nontaxane microtubule dynamics inhibitor used for the treatment of advanced breast cancer, inhibits EMT changes in triple-negative breast cancer cells. We examined its ability to inhibit tumor progression and EMT changes resulting from the interaction between gastric cancer cells and HPMCs and to act synergistically with 5-fluorouracil (5-FU), a key drug for gastric cancer. Materials and methods: Proliferation of gastric cancer cells and HPMCs isolated from healthy omentum was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Following gastric cancer cell/HPMC coculture, EMT markers were detected by immunofluorescence, immunohistochemistry, and Western blotting; invasion assays were performed; and TGF-β and Smad phosphorylation were assessed by Western blotting and enzyme-linked immunosorbent assay. A mouse fibrotic tumor xenograft model was established using gastric cancer cell/HPMC cocultures. The effect of eribulin and/or 5-FU was tested in each case. Results: Eribulin significantly suppressed gastric cancer cell proliferation and EMT changes in MKN-45 gastric cancer cells and HPMCs induced by their interaction in vitro. Eribulin inhibited EMT at much lower concentrations (≥0.5 nM for MKN-45 and ≥0.1 nM for HPMCs) than its half maximal inhibitory concentrations (2.2 nM for MKN-45 and 8.1 nM for HPMCs), and this resulted, at least partly, from the downregulation of TGF-β/Smad signaling. Eribulin administration of ≥0.1 mg/kg suppressed tumor progression (0.1 mg/kg, p =0.02), and fibrosis was inhibited by lower dose (0.05 mg/kg, p =0.008) in the xenograft model. Furthermore, 0.05 mg/kg administration with 5-FU brought about synergistic antitumor effects ( p =0.006). Conclusion: Low-dose eribulin combined with 5-FU might be a promising therapy for peritoneal dissemination in gastric cancer. Keywords: peritoneal dissemination, cancer–stromal interaction, human peritoneal mesothelial cell, TGF-β, Smad, synergism
Expert Opinion on Biological Therapy · 2008 · 14 citations
The evolving role of catumaxomab in gastric cancer
AbstractBACKGROUND: Gastric cancer is a condition with a high medical need. Even after R0 resection the rate of peritoneal and other distant site recurrences is high. Novel therapeutic approaches include trifunctional antibodies (trAb) that recruit and activate different types of immune effector cells at the tumour site. The trAb catumaxomab has dual antigen specificity for epithelial cell adhesion molecule and CD3 and binds to Fcgamma-receptor-positive accessory cells. Intraperitoneal administration of catumaxomab in patients with malignant ascites due to epithelial cancer significantly increased puncture-free survival. OBJECTIVE: To review the mode of action of catumaxomab and describe clinical data regarding the emerging role of catumaxomab in the treatment of patients with gastric cancer. A summary of completed and ongoing clinical trials including patients with gastric cancer is given. CONCLUSION: Catumaxomab is a promising approach in the treatment of patients with gastric cancer.
Evolving Standards of Care in Advanced Gastric Cancer
AbstractDespite its decreasing incidence in western countries, the care of gastric cancer remains a concern, as many patients are diagnosed with advanced disease. Whereas localized gastric cancer has benefited from advances in surgical management and perioperative chemotherapy, patients with unresectable or metastatic disease have a poor prognosis. However, advances in chemotherapy have still arisen, with the onset of more convenient and active schedules of treatment, but no significant breakthrough has been achieved in terms of survival. Recent trials in advanced gastric cancer have been focusing on targeted therapies. This article aims to focus on the current state of the art in terms of chemotherapy for advanced gastric cancer, as well as to describe and explain the rationale and hopes for newer therapies that are currently under investigation.
AbstractDespite significant therapeutic progress, gastric cancer remains among the deadliest forms of cancer encountered in clinical practice, and this remains true even in the context of declining incidence. Outcomes in advanced disease remain poor and therapy is rarely curative in this setting. Different therapies have developed in the hopes of altering nearly uniformly poor outcomes.
[Progress in study on the treatment of gastric cancer with docetaxel].
AbstractGastric cancer is one of the most common malignant gastrointestinal tumors. Docetaxel alone or combination with other drugs can attenuate the progress of disease, prolong the overall response rate and the median overall survival rate in advanced gastric cancer. However, the incidence of toxicities is high. Moreover, there is no uniform standard for dosage and course for docetaxel treatment. Currently, its efficacy is not definite.
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.
