DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for childhood kidney cell carcinoma — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChildhood kidney cell carcinoma maps to a 1-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
approvedDoxorubicinApproved drug
Structures already discussed alongside childhood kidney cell carcinoma in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
dicer 1, ribonuclease III (DICER1) — DICER1 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.
Loading structure…
helix sheet apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7XW2 · 3.04 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Childhood renal cell carcinoma is a rare kidney cancer most common in teenagers and young adolescents. A 2020 narrative review of series with at least 10 paediatric patients states that clinical, molecular and histological features in children differ from adult RCC, but treatment strategies are still based on adult data. The review does not report survival or response rates from any single trial or pooled analysis.
A 1995 report from the Mersey Regional Cancer Registry recorded only one case of renal carcinoma in a patient under 20 years over 19 years. The authors note that only about 177 cases had been reported in English literature at that time, and they stress that long-term follow-up is needed to assess treatment results.
A 2007 laboratory study tested the combination of doxorubicin with HGS-ETR1, a monoclonal antibody targeting death receptor 4, in human renal cell carcinoma cell lines. In the ACHN line, combining HGS-ETR1 with 5-fluorouracil, vinblastine or gemcitabine did not overcome resistance. However, doxorubicin plus HGS-ETR1 produced synergistic cytotoxicity in ACHN, Caki-1, and five freshly derived renal cell carcinoma cultures. Synergy was also seen with doxorubicin derivatives epirubicin, pirarubicin and amrubicin. Sequential treatment — doxorubicin followed by HGS-ETR1 — induced significantly more cytotoxicity than the reverse order or simultaneous treatment (p<0.05). Doxorubicin increased cell surface expression of death receptor 4 and the combination activated caspases 8, 9, 6 and 3. This is a preclinical study; no children were treated.
What is missing: prospective paediatric trials with survival endpoints, any clinical trial testing doxorubicin plus a death receptor agonist in children with RCC, and molecular stratification that accounts for the differences between paediatric and adult disease. Funding for such trials and international collaboration to recruit enough patients remain 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.
Cancers · 2020 · 41 citations · open access
Characteristics and Outcome of Children with Renal Cell Carcinoma: A Narrative Review
AbstractPediatric renal cell carcinoma (RCC) is a rare type of kidney cancer, most commonly occurring in teenagers and young adolescents. Few relatively large series of pediatric RCC have been reported. Knowledge of clinical characteristics, outcome and treatment strategies are often based on the more frequently occurring adult types of RCC. However, published pediatric data suggest that clinical, molecular and histological characteristics of pediatric RCC differ from adult RCC. This paper summarizes reported series consisting of ≥10 RCC pediatric patients in order to create an up-to-date overview of the clinical and histopathological characteristics, treatment and outcome of pediatric RCC patients.
Enhancement of Death Receptor 4 Mediated Apoptosis and Cytotoxicity in Renal Cell Carcinoma Cells by Subtoxic Concentrations of Doxorubicin
AbstractPURPOSE: TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) triggers apoptosis in various tumor cells by engaging death receptors 4 and 5. We investigated the effect of chemotherapeutic agents on death receptor 4 mediated apoptosis in human renal cell carcinoma cells using HGS-ETR1, which is a human monoclonal agonistic antibody specific for death receptor 4. MATERIALS AND METHODS: Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Synergy was assessed by isobolographic analysis. RESULTS: Treatment of the ACHN human renal cell carcinoma cell line with HGS-ETR1 combined with 5-fluorouracil, vinblastine or gemcitabine did not overcome resistance to these agents. However, treatment with HGS-ETR1 combined with doxorubicin had a synergistic cytotoxic effect. Synergy was also achieved in another human renal cell carcinoma cell line, Caki-1, and in 5 freshly derived renal cell carcinoma cell cultures. A synergistic effect was also observed with HGS-ETR1 combined with the doxorubicin derivatives epirubicin, pirarubicin or amrubicin. The synergy achieved in cytotoxicity with HGS-ETR1 and doxorubicin was also achieved in apoptosis. Sequential treatment with doxorubicin followed by HGS-ETR1 induced significantly more cytotoxicity than reverse treatment or simultaneous treatment (p<0.05). Doxorubicin remarkably increased the cell surface expression of death receptor 4 in renal cell carcinoma cells. The combination of doxorubicin and HGS-ETR1 significantly activated the caspase cascade, including caspase-8, 9, 6 and 3, which are the downstream molecules of death receptors. CONCLUSIONS: These findings indicate that doxorubicin sensitizes renal cell carcinoma cells to death receptor 4 mediated apoptosis through the induction of death receptor 4 and the activation of caspases, suggesting that combination therapy of doxorubicin and HGS-ETR1 might be effective as renal cell carcinoma therapy.
Long-term survival in children with renal carcinoma: Report of two surgically treated cases
AbstractAbstract Renal carcinoma in childhood is rare. Approximately 177 cases have been reported in the English literature and 71 in the Japanese literature1, 2. The Mersey Regional Cancer Registry has recorded only one case of renal carcinoma in a patient below the age of 20 years in the 19-year period since 1975. The annual incidence of this disease in children in the USA is four per 1 million3. Onus rests on authors to report the long-term follow-up of such cases, otherwise it is difficult to assess the results of treatment1.
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.
