DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for esophageal cancer — screening already-approved drugs against its 44-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEsophageal cancer maps to a 44-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 esophageal cancer 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 2003 microarray study of 588 cancer-related genes in human esophageal squamous cell carcinoma found more than 100 genes up- or down-regulated across stages from basal cell hyperplasia to late cancer. P160ROCK and JNK2 were activated in early carcinogenesis. A 2019 multi-omics analysis of The Cancer Genome Atlas data reported that GNGT2 expression was significantly upregulated in esophageal cancer patient samples and cell lines, and that GNGT2 promoted proliferation of esophageal cancer cell lines in a CCK-8 assay. No survival data or response rates were given in either study.
A 2013 retrospective study in north-west Iran included 255 patients (213 squamous cell, 12 adenocarcinoma; median age 68). 166 received chemoradiotherapy alone (CRT) and 59 received surgery plus postoperative chemoradiotherapy (S/CRT). Chemotherapy was cisplatin and 5-fluorouracil; median radiation dose was 45 ± 13.6 Gy. Median survival was 13.5 months (95% CI 11–15). One-, two-, and three-year overall survival was 57%, 21%, and 16%. 158 patients died, 97 were alive at analysis. Multivariate analysis identified radiation dose and fractionation as the only independent predictor of survival. The authors concluded that a significant need remains for new drugs and therapeutic approaches that can substantially impact survival.
A 2022 narrative review of radiation oncology for esophageal cancer states that for resectable disease, neoadjuvant chemoradiation followed by surgery has been the standard of care over the past decade. For patients with incomplete response to neoadjuvant chemoradiation, adjuvant immunotherapy has recently been established. For locally advanced disease, recent studies failed to show a benefit with radiation dose escalation in an unselected population. Ongoing studies are examining whether perioperative chemotherapy may be equivalent to neoadjuvant chemoradiation in resectable adenocarcinoma, and whether proton beam therapy or combining immunotherapy or targeted therapies with chemoradiation can improve outcomes. A separate 2022 review notes that immunotherapy has been progressively approved as first- and second-line treatment for esophageal cancer, but provides no new trial data.
What is still missing: prospective randomised trials that stratify patients by molecular subtype or by response to induction therapy, adequately powered to detect survival differences. The 2003 and 2019 gene-expression studies identified candidate genes but did not test them as therapeutic targets in patients. The 2013 Iranian study was retrospective and underpowered for subgroup comparisons. No abstract reports a completed phase 3 trial showing a survival gain from a repurposed drug in an unselected population.
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 Gastroenterology · 2003 · 66 citations · open access
Gene expression profiles at different stages of human esophageal squamous cell carcinoma
AbstractAIM: To characterize the gene expression profiles in different stages of carcinogenesis of esophageal epithelium. METHODS: A microarray containing 588 cancer related genes was employed to study the gene expression profile at different stages of esophageal squamous cell carcinoma including basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis was performed to search the genes which were important in carcinogenesis. RESULTS: More than 100 genes were up or down regulated in esophageal epithelial cells during the stages of basal cell hyperplasia, high-grade dysplasia, carcinoma in situ, early and late cancer. Principle component analysis identified a set of genes which may play important roles in the tumor development. Comparison of expression profiles between these stages showed that some genes, such as P160ROCK, JNK2, were activated and may play an important role in early stages of carcinogenesis. CONCLUSION: These findings provided an esophageal cancer-specific and stage-specific expression profiles, showing that complex alterations of gene expression underlie the development of malignant phenotype of esophageal cancer cells.
Japanese Journal of Clinical Oncology · 2009 · 29 citations · open access
A Phase II Study of Paclitaxel and Nedaplatin as First-line Chemotherapy in Patients with Advanced Esophageal Cancer
AbstractOBJECTIVE: The aim of this study was to assess the efficacy and toxicity of the combination of paclitaxel and nedaplatin as a first-line chemotherapy for patients with advanced esophageal cancer. METHODS: Patients with advanced esophageal cancer received 175 mg/m(2) of paclitaxel over a 3 h infusion, followed by nedaplatin 80 mg/m(2) in a 1 h infusion on day 1 every 3 weeks until the documented disease progression, unacceptable toxicity or patient's refusal. RESULTS: Between March 2005 and December 2007, 48 patients entered in the study. Forty-six (95.8%) of the 48 patients were assessable for response. The overall response rate was 41.7% (95% CI, 27.8-55.7%) with 2 complete responses and 18 partial responses. The median follow-up period was 20.5 months (range, 12.5-27.2 months). The median overall time to progression and overall survival (OS) were 6.1 months (95% CI, 4.8-7.4 months) and 11.5 months (95% CI, 9.1-13.9 months), respectively. The estimate of OS at 12 and 24 months was 43.8% (95% CI, 29.7-77.8%) and 10.4% (95% CI, 1.8-19.1%), respectively. Most patients experienced anemia, during their course of therapy with 6 (13.0%) patients for grade 3/4 anemia, and grade 1 or 2 anemia was detected in 23 (50%) patients. Grade 3 leucopenia, neutropenia and thrombocytopenia were documented in 8 (17.4%), 9 (17.4%) and 2 (4.3%) patients, respectively. Grade 3 nausea and vomiting were detected in 3 (6.5%) and 2 (4.3%) patients, respectively. Two patients (4.3%) were hospitalized because of treatment-related complications. The treatment was well tolerated and no toxic death occurred. CONCLUSIONS: Combination of paclitaxel and nedaplatin is a tolerated treatment modality with promising activity in previously untreated advanced esophageal cancer.
World Journal of Gastroenterology · 2019 · 16 citations · open access
Comprehensive multi-omics analysis identified core molecular processes in esophageal cancer and revealed GNGT2 as a potential prognostic marker
AbstractBACKGROUND: Esophageal cancer is one of the most poorly diagnosed and fatal cancers in the world. Although a series of studies on esophageal cancer have been reported, the molecular pathogenesis of the disease remains elusive. AIM: To investigate comprehensively the molecular process of esophageal cancer. METHODS: Differential expression analysis was performed to identify differentially expressed genes (DEGs) in different stages of esophageal cancer from The Cancer Genome Atlas data. Exacting gene interaction modules were generated, and hub genes in the module interaction network were found. Further, through survival analysis, methylation analysis, pivot analysis, and enrichment analysis, some important molecules and related functions/pathways were identified to elucidate potential mechanisms in esophageal cancer. RESULTS: expression was significantly upregulated in esophageal cancer patient samples and cell lines. Moreover, cell counting kit-8 assay revealed that GNGT2 could promote the proliferation of esophageal cancer cell lines. CONCLUSION: This study not only revealed the potential regulatory factors involved in the development of esophageal cancer but also deepens our understanding of its underlying mechanism.
Tsunami of Immunotherapies in the Management of Esophageal Cancer
AbstractEsophageal cancer (EC) is relatively frequent and highly lethal cancer, being the sixth most common cause of cancer death worldwide. The progressive approvals of immunotherapy as first-line and second-line treatment options have paved the way for an evolving new approach to the treatment of this disease. Management of esophageal cancer is challenging and requires a multimodality approach. Treatment options include surgery, chemoradiotherapy and, recently, immunotherapy. The newest guidelines and FDA approvals regarding immunotherapy for esophageal cancer are reviewed here.
Journal of Thoracic Disease · 2022 · 2 citations · open access
Current landscape of radiation oncology in esophageal cancer: a narrative review
AbstractBackground and Objective: Esophageal cancer is an aggressive disease that is the sixth leading cause of cancer-related death worldwide. The overall treatment paradigm for esophageal cancer has changed considerably over the past decade. This narrative review aims to summarize the current landscape of radiation oncology for esophageal cancer. Methods: A systematic search of the MEDLINE/PubMed database and Clinicaltrials.gov was performed, focusing on studies published within the last 10 years. Our search queried "esophageal cancer [AND] neoadjuvant radiation" as well as "locally advanced esophageal cancer [AND] definitive radiation". Our search resulted in 298 total references. These were manually reviewed, and only 58 references were within our scope of interest ranging from 2012-2022. Key Content and Findings: For resectable esophageal cancer, neoadjuvant chemoradiation followed by surgery has been defined as the standard of care over the past decade. In patients with incomplete response to neoadjuvant chemoradiation, the benefit of immunotherapy in the adjuvant setting has recently been established. Ongoing studies are examining whether perioperative chemotherapy may be equivalent to neoadjuvant chemoradiation in resectable esophageal adenocarcinoma. For locally advanced esophageal cancer, recent studies have failed to show a benefit with radiation dose escalation in an unselected population, although the use of early positron emission tomography (PET) response to guide dose escalation is currently being studied. Other ongoing studies aiming to improve outcomes in locally advanced esophageal cancer involve using proton beam therapy to reduce toxicity and combining immunotherapy or targeted therapies with chemoradiation to amplify response. Conclusions: Recent advances in radiation oncology may continue to improve outcomes for patients with esophageal cancer.
Asian Pacific Journal of Cancer Prevention · 2013 · 2 citations · open access
Impact of Postoperative Chemoradiotherapy and Chemoradiotherapy Alone for Esophageal Cancer in North-West Iran
AbstractBACKGROUND: To investigate the role of surgical treatment for locally advanced esophageal cancer, we compared the outcomes of chemoradiotherapy alone (CRT) to postoperative chemoradiotherapy (S/CRT), using, Regional Radiotherapy Center, database. MATERIALS AND METHODS: This retrospective study was conducted in North-West of Iran, included of 255 consecutive patients with esophageal cancer. Eligible operable and non-operable, were treated with S/CRT and CRT respectively. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. RESULTS: From March 2006 to March 2011 255 patients: male/female 129/96, median age 68 (35-90), squamous/adeno 213/12, received CRT /S+CRT 166/59, median radiation dose 45 ± 13.6 Gy, Median survival 13.5 (11-15), overall survival (OS) One/ Two/Three 57/21/16%, Died/alive 158/97, Univariate analysis prognostic factors: age/stag/differentiation/dose of RT/fraction/treatment, Multivariate analysis predictor factor: dose of RT/fraction. CONCLUSIONS: Although this treatment offers some possibility for improvement of patients with esophageal cancer, there remains a significant need for development of new drug and new therapeutic approaches that can substantially impact survival.
AbstractDespite therapy, most patients diagnosed with esophageal cancer in 2004 will die from their disease. Surgery and radiation have been the historical treatments of choice for esophageal cancer. However, in an effort to improve outcome, combination therapies have emerged with concurrent chemoradiotherapy, neoadjuvant chemotherapy and chemoradiotherapy, and adjuvant chemotherapy and chemoradiotherapy. Strong proponents for specific individual therapeutic approaches exist, as does controversy because no optimal treatment plan for esophageal cancer has clearly emerged.
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.
