DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Ampulla of Vater Carcinoma — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAmpulla of Vater Carcinoma maps to a 46-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 ampulla of vater 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
transforming growth factor beta receptor 2 (TGFBR2) — TGFBR2 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 6-methoxypyridin-3-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5QIN · 1.57 Å · ligand N-{4-[3-(6-methoxypyridin-3-yl)-1H-pyrrolo[3,2-b]pyridin-2-yl]pyridin-2-yl}acetamide (J2V). Experimental structure, not a prediction.
What the evidence adds up to
A 20-year single-institution series of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia (1981–2002) reported that 64 underwent pancreatoduodenectomy and 30 received palliative treatment (surgical in 5, endoscopic in 25). Median survival was 9 months for non-resected patients and 54 months for resected patients; overall 5-year survival after pancreatoduodenectomy was 64.4%. Surgical morbidity was 34.3% and postoperative mortality 9.3%, with no deaths among the last 38 patients treated. In multivariate analysis only depth of tumour infiltration influenced survival.
A prospective single-arm study from 1995–1999 gave 12 patients with unfavourable ampullary carcinoma (defined as involved lymph nodes, involved margins, poor differentiation, tumour >2 cm, or neurovascular invasion) adjuvant chemoradiotherapy after pancreatoduodenectomy: 45 Gy radiotherapy plus protracted venous infusion fluorouracil (225–250 mg/m² per day, 7 days per week) for 5 weeks. All 12 completed treatment; one had a one-week interruption for grade III nausea/vomiting, and no grade IV or V toxicity occurred. At median follow-up of 24 months, 8 of 12 were alive and disease-free, one was alive with recurrence, and three had died of liver metastases. Actuarial 2-year overall survival was 89%, median survival 34 months. The authors note that median survival was better than in a parallel cohort of resected high-risk pancreatic cancer patients given the same regimen (34 vs 14 months, p<0.004).
A 2019 case report describes a 68-year-old woman with ampullary carcinoma and lymph node plus multiple liver metastases who received gemcitabine plus cisplatin for 19 months. Imaging showed the primary tumour and liver metastases were difficult to detect, and enlarged lymph nodes had shrunk. She underwent surgical resection with curative intent; pathological examination of the resected specimen found no residual tumour. The postoperative course was uneventful and she remained free of recurrent disease at 10 months follow-up.
A retrospective study of 46 patients who had surgery for ampullary carcinoma between 2005 and 2022 reported 5-year overall survival of 63.1% and relapse-free survival of 61.7% over a median observation of 33.7 months. Recurrence occurred in 14 patients (30%), seven within one year. Fifteen patients received adjuvant chemotherapy (S-1 in 11, gemcitabine in 4). The 5-year overall survival with and without adjuvant chemotherapy was 70.3% vs 48.2% (p=0.093); 5-year relapse-free survival was 72.5% vs 42.8% (p=0.058). In multivariate analysis, only lymph node positivity was significantly associated with relapse-free survival (HR 3.53; 95% CI 0.99–12.6; p=0.03). Among node-positive patients, 5-year overall survival was 77.1% vs 42.7% (p=0.04) and 5-year relapse-free survival 80.4% vs 32.1% (p=0.004). The authors conclude that adjuvant chemotherapy showed a tendency to be effective, particularly in node-positive cases, but the differences did not reach statistical significance in the overall comparison.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
World Journal of Surgery · 2005 · 87 citations
Pancreatoduodenectomy for Tumors of Vater’s Ampulla: Report on 94 Consecutive Patients
AbstractEvaluation of prognostic factors of adenocarcinoma of Vater's ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival. Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.
Adjuvant Chemoradiotherapy for "Unfavorable" Carcinoma of the Ampulla of Vater
AbstractHYPOTHESES: Adjuvant chemoradiotherapy decreases the risk of local recurrence in patients with adenocarcinoma of the ampulla of Vater and high-risk features. Adjuvant chemoradiotherapy for this population can be administered safely and without much morbidity. DESIGN: Controlled, prospective, single-arm study. SETTING: Tertiary care referral hospital. PATIENTS: From June 1995 to March 1999, 12 patients (7 men and 5 women; median age, 66 years; age range, 38-78 years) with "unfavorable" ampullary carcinoma were treated with adjuvant chemoradiotherapy. All patients underwent pancreaticoduodenectomy, and all pathologic findings were confirmed at Stanford University Medical Center, Stanford, Calif. Unfavorable features were defined as involved lymph nodes (n = 10), involved surgical margins (n = 1), poorly differentiated histological features (n = 3), tumor size greater than 2 cm (n = 6), or the presence of neurovascular invasion (n = 4). INTERVENTIONS: Four to 6 weeks after undergoing pylorus-preserving pancreaticoduodenectomy with regional lymphadenectomy, patients began adjuvant chemoradiotherapy consisting of concurrent radiotherapy (45 Gy) and fluorouracil by protracted venous infusion (225-250 mg/m(2) per day, 7 days per week) for 5 weeks. MAIN OUTCOME MEASURES: Local recurrence, distant recurrence, overall survival rate, and treatment-related toxic effects. RESULTS: All patients completed the prescribed treatment course. Toxic effects were assessed twice a week during treatment and graded according to the National Cancer Institute Common Toxicity Criteria Scale. One patient required a treatment interruption of 1 week for grade III nausea/vomiting. No grade IV or V toxic effects were observed. At median follow-up of 24 months (range, 13-50 months), 8 of 12 patients were alive and disease free. One patient was alive but had disease recurrence. Three patients died of this disease (liver metastases). Actuarial overall survival at 2 years was 89%, and median survival was 34 months. One surviving patient developed a local recurrence and a lung lesion. Actuarial overall survival and median survival were better than in a parallel cohort with resected high-risk pancreatic cancer (n = 26) treated with the same adjuvant chemoradiotherapy regimen (median survival, 34 vs 14 months; P<.004). CONCLUSIONS: Adjuvant chemoradiotherapy for carcinoma of the ampulla of Vater is well tolerated and might improve control of this disease in patients with unfavorable features.
Surgical Case Reports · 2019 · 3 citations · open access
Conversion surgery for initially unresectable carcinoma of the ampulla of Vater following pathological complete response to chemotherapy: a case report
AbstractBACKGROUND: Carcinoma of the ampulla of Vater with distant metastases is regarded as unresectable. Systemic chemotherapy is basically the treatment of choice for such tumors. CASE PRESENTATION: A 68-year-old woman was referred to our hospital and diagnosed with carcinoma of the ampulla of Vater with lymph node and multiple liver metastases. She underwent systemic chemotherapy with a combination of gemcitabine and cisplatin. After 19 months of treatment, the primary tumor and liver metastases were difficult to detect on follow-up images. Shrinkage of the enlarged lymph nodes was also confirmed. Surgical resection was performed with curative intent after a multidisciplinary meeting. Pathological examination of the resected specimen showed no residual tumors. Systemic chemotherapy achieved a pathological complete response. The postoperative course was uneventful, and the patient remained free of recurrent disease at 10 months of follow-up. CONCLUSION: This case shows the possibility of conversion surgery after systemic chemotherapy for carcinoma of the ampulla of Vater.
Analysis of the treatment outcome of ampulla of Vater carcinoma and the usefulness of postoperative adjuvant chemotherapy.
Abstract692 Background: Patients with ampulla of Vater carcinoma with lymph node metastasis reportedly have a poor prognosis and require postoperative adjuvant therapy. However, due to the small number of published cases, the efficacy of postoperative adjuvant therapy has not yet been established with a high level of evidence. Objective: The aim of this study was to describe the outcome of patients surgically treated for ampulla of Vater carcinoma in our department, evaluate the effectiveness of adjuvant chemotherapy (AC), and clarify which patient groups may benefit from AC. Methods: The study cohort comprised 46 patients who underwent surgery for ampulla of Vater carcinoma in our department from October 2005 to March 2022. We evaluated the clinicopathological background characteristics (tumor size, gross morphology, pancreatic/duodenal invasion, peripancreatic head lymph node metastasis), overall survival (OS), and relapse-free survival (RFS), and compared the OS and RFS in patients with versus without AC. We then analyzed the factors related to the long-term outcome of patients treated for ampulla of Vater carcinoma. Results: During a median observation period of 33.7 months, the 5-year OS and RFS were 63.1% and 61.7%, respectively. Recurrence was observed in 14 patients (30%), with recurrence occurring less than 1 year postoperatively in seven patients (15%). Fifteen patients received AC (chemotherapy regimen: S-1 in 11 patients, GEM in four). The 5-year OS rates with and without AC were 70.3% and 48.2%, respectively (p=0.093). The 5-year RFS rates with and without AC were 72.5% and 42.8%, respectively (p=0.058). Univariate analysis of the total patient cohort showed that the factors related to 5-year RFS were pancreatic invasion (p=0.01), duodenal invasion (p=0.03), and N+ (p=0.004). In multivariate analysis, the only factor related to 5-year RFS was N+ (HR 3.53; 95% CI, 0.99–12.6; p=0.03). The 5-year OS rates in patients with and without N+ were 77.1% and 42.7%, respectively (p=0.04). The 5-year RFS rates in patients with and without N+ were 80.4% and 32.1%, respectively (p=0.004). Conclusions: AC showed a tendency to be effective in preventing postoperative recurrence of ampulla of Vater carcinoma. AC may be particularly beneficial in N+ cases.
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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