DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for adenocarcinoma — screening already-approved drugs against its 42-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAdenocarcinoma maps to a 42-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
approvedCabazitaxelApproved drug
Structures already discussed alongside adenocarcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
dihydrofolate reductase (DHFR) — DHFR is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has nadph dihydro-nicotinamide-adenine-dinucleotide phosphate bound in it, shown as sticks.
Loading structure…
helix sheet ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4M6J · 1.201 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
A National Cancer Database study of 1729 patients with stage 1–3 anal adenocarcinoma diagnosed between 2004 and 2015 reported a median overall survival of 55 months and a five-year survival rate of 55% for the whole group. Among these patients, 1028 received surgery as upfront management and 701 received definitive chemoradiation alone. Patients treated without surgery had worse overall survival: median 45 months versus 87 months, with five-year survival rates of 42% and 55% respectively, favouring incorporation of surgery. When analysed by treatment sequence, median survival was 78 months for surgery alone, 83 months for surgery followed by adjuvant chemoradiation, 92 months for neoadjuvant chemoradiation followed by surgery, and 46 months for chemoradiation alone. Propensity score-adjusted multivariable analysis identified older age, grade 3 histology, high comorbidity score, and lack of surgery as predictors of worse outcome.
A separate National Cancer Database study of 19,120 patients with adenocarcinoma in villous adenoma diagnosed between 2004 and 2020 found that males had an 18% higher risk of mortality compared to females (hazard ratio 0.82; 95% CI 0.79–0.86). Black patients had a 22% increased mortality risk relative to White patients (HR 1.22; 95% CI 1.14–1.30). Patients in lower-income brackets (below $46,277 versus $74,063 or more) had a hazard ratio of 0.88 (95% CI 0.82–0.94), and those with Medicare or Medicaid insurance faced increased mortality compared to those with private insurance (Medicare HR 1.26; 95% CI 1.19–1.33; Medicaid HR 1.57; 95% CI 1.41–1.74). Higher Charlson-Deyo comorbidity scores were associated with worse ten-year survival (25.9% for CD 2; 17.8% for CD 3), and stage IV disease carried a hazard ratio of 9.23 (95% CI 8.32–10.24). Primary radiation increased mortality risk by 24% (HR 1.24; 95% CI 1.15–1.33), while neoadjuvant radiation and adjuvant chemotherapy decreased mortality risk by 39% (HR 0.61; 95% CI 0.54–0.69) and 26% (HR 0.74; 95% CI 0.68–0.81), respectively.
A 2017 review of molecular targeted therapy for adenocarcinoma of the esophagogastric junction notes that surgery remains the main treatment but that surgery alone sometimes results in poor prognosis. The review lists molecular targets under investigation — vascular endothelial growth factor, hepatocyte growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor 2, and human epidermal growth factor receptor-2 — and describes their prospects as broad but does not report any clinical trial results, response rates, or survival data from those approaches.
What is still missing are prospective trials that validate the retrospective findings, particularly regarding the optimal sequencing of surgery and chemoradiation for anal adenocarcinoma and the role of adjuvant therapies in adenocarcinoma in villous adenoma. No randomised data exist to confirm whether the survival differences seen in registry analyses are due to treatment effects or patient selection. The molecular targeted therapy review highlights candidate targets but provides no evidence from completed trials that any such agent improves outcomes in adenocarcinoma of the esophagogastric junction. Funding for prospective, stratified studies and for trials that address the socioeconomic and racial disparities identified in the registry data remains absent.
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 Medicine · 2019 · 26 citations · open access
Anal adenocarcinoma: Treatment outcomes and trends in a rare disease entity
AbstractIMPORTANCE: Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage. OBJECTIVE: We conducted this National Cancer Database (NCDB)-driven retrospective study to analyze treatment trends and outcomes in the current time from 2004 to 2015 with respect to chemoradiation and surgery. DESIGN: Retrospective NCDB tumor registry data review-using propensity score-adjusted multivariable analyses for survival. SETTING: Database review. PARTICIPANTS: We selected for patients listed in the NCDB with AJCC stage 1-3 anal adenocarcinoma diagnosed between 2004 and 2015 and selected out patients with undocumented/stage 4 disease, those with radiation outside the pelvis, not treated with systemic therapy and patients lost to follow-up. EXPOSURE(S): None. MAIN OUTCOMES AND MEASURES: Overall survival and use of surgery in the up-front management of anal adenocarcinoma. RESULTS: Of the 1729 patients eligible in this study, 1028 were treated with surgery as up-front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5-year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (P < 0.0001) with 5-year survival rates of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively. Propensity score-adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome. CONCLUSIONS AND RELEVANCE: The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior to the year 2000 for surgery to be included in the definitive management of anal adenocarcinoma.
A multicentre, phase II study with cabazitaxel in previously treated patients with advanced or metastatic adenocarcinoma of the oesophagogastric junction and stomach (CABAGAST).
Abstract4054 Background: This is a single-arm study to determine prolonged ( > = 4 months) disease control rate with cabazitaxel administered in second- (or later) setting for patients with advanced or metastatic adenocarcinoma of the esophagogastric junction (EGJ) and stomach. Methods: 65 patients with advanced EGJ and stomach cancer were treated with 20mg/m 2 Cabazitaxel every 3 weeks for a maximum of 6 cycles. Main objective of the study was a prolonged Disease Control Rate (pDCR: CR, PR or SD lasting at least 4 months). Secondary Outcome Measures were overall survival (OS), progression-free survival (PFS), response rate by subgroup (with vs without previous treatment with a taxane) and toxicity. Patients were assessed for tumor response every 6 weeks during therapy and during follow-up (up to 12 months). Results: 65 patients (median age: 63, range 31-86 years) were assigned. Median no. of prior therapies was 2. 80% had received prior taxane therapy. Patients received a median of 2 cycles of cabazitaxel. Efficacy results are shown for the per protocol (PP) population. pDCR rate was 12.7%, (95%CI: 5,3%- 24.5%). pDCR was 20.0% in 2 nd line patients (95%CI: 6.8%-40.7%) and 30.0% (95%CI: 6.7%-65.2%) in all lines in patients without prior taxane use. Response Rate was 5.5% (95%CI: 1.1%-15.1%) in total PP and 20.0% in the population without prior taxane use. Median OS was 4.6 months (7.4 months without prior taxane vs 3.8 months with prior taxane). Median PFS was 1.38 months (95%CI: 1.28- 1.87) with and 2.01 months (95%CI: 0.20- 4.67) without prior taxane use. Most common grade 3/4 toxicities were neutropenia in 13% of the patients, pain (12%), leucopenia (10%), anemia (10%), fatigue (10%) and nausea (10%). Conclusions: Cabazitaxel is active in heavily pretreated patients with metastatic and advanced esophagogastric junction and gastric adenocarcinoma. Toxicity is moderate. Patients without prior taxane use derived more benefit from Cabazitaxel. Clinical trial information: NCT01956149.
Anal adenocarcinoma: Treatment outcomes and trends in a rare disease entity.
Abstract538 Background: Primary Adenocarcinoma of the rectum is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage. We conducted this NCDB-driven, retrospective study to analyze treatment trends and outcomes in the current time from 2004-2015 with respect to chemoradiation and surgery. Methods: We queried the NCDB for with AJCC stage 1-3 anal adenocarcinoma diagnosed between 2004-2015. Propensity score-matched multivariable cox regression analysis determined the association of incorporation of surgery into the definitive management of anal adenocarcinoma on survival. Results: Of the 1729 patients eligible patients in this study, 1028 were treated with surgery as up front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5 year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (p < .0001) with 5 year survivals of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively (p < 0.0001). Propensity score adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome. Conclusions: The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior for surgery to be included in the definitive management of anal adenocarcinoma.
A National Cancer Database Study on the Demographic, Prognostic, and Socioeconomic Factors Affecting Survival in Adenocarcinoma in Villous Adenoma
AbstractPURPOSE: Adenocarcinoma in villous adenoma is a rare malignancy arising from adenomatous polyps with a high villous content. This study aims to identify the demographic, prognostic, and socioeconomic factors influencing overall survival using data sourced from the National Cancer Database (NCDB). METHODS: Patients diagnosed with adenocarcinoma in villous adenoma were identified from the NCDB between 2004 and 2020. Kaplan-Meier curves, multivariable Cox proportional hazards models, life tables, and log-rank tests were used to assess the impact of variables such as age, sex, NCDB tumor stage, Charlson-Deyo (CD) comorbidity score, primary therapies, adjuvant therapies, and socioeconomic factors on survival. RESULTS: This cohort of 19,120 patients with adenocarcinoma in villous adenoma revealed multiple statistically significant factors affecting survival. Demographically, males had an 18% higher risk of mortality compared to females (hazard ratio (HR): 0.82; 95% confidence interval (CI): 0.79-0.86; p<0.001), older age (76-100 age group, five years: 45.3%; 10 years: 20.7%; p<0.001) correlated with poorer outcomes, and Black patients had a 22% increased mortality risk relative to White patients (HR: 1.22; 95% CI: 1.14-1.30; p<0.001). Socioeconomically, patients in lower-income brackets (<$46,277 vs. ≥$74,063, HR: 0.88; 95% CI: 0.82-0.94; p<0.001) and those with Medicare or Medicaid insurance faced increased mortality risks compared to those with private insurance (Medicare, HR: 1.26; 95% CI: 1.19-1.33; p<0.001; Medicaid, HR: 1.57; 95% CI: 1.41-1.74; p<0.001). Disease and comorbidity factors showed that higher CD comorbidity scores (10-year survival: 25.9% for CD 2; 17.8% for CD 3; p<0.001) and stage IV disease (HR: 9.23; 95% CI: 8.32-10.24; p<0.001) were associated with poorer outcomes. Regarding treatment, primary radiation increased mortality risk by 24% (HR: 1.24; 95% CI: 1.15-1.33; p<0.001), while neoadjuvant radiation and adjuvant chemotherapy decreased mortality risk by 39% (HR: 0.61; 95% CI: 0.54-0.69; p<0.001) and 26% (HR: 0.74; 95% CI: 0.68-0.81; p<0.001), respectively. CONCLUSION: Adenocarcinoma in villous adenoma outcomes is influenced by age, sex, race, NCDB cancer stage, comorbidities, and treatment type. Surgical intervention remains the primary treatment and confers improved survival outcomes, emphasizing the importance of early detection and treatment. Further research, including prospective studies, is needed to validate these findings, investigate the mechanisms underlying observed disparities, and optimize treatment strategies, particularly the role of adjuvant therapies.
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.
