DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for brain stem astrocytic neoplasm — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBrain stem astrocytic neoplasm maps to a 3-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 brain stem astrocytic neoplasm 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
activin A receptor type 1 (ACVR1) — ACVR1 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 3,4,5-trimethoxyphenyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6EIX · 2.3 Å · ligand 3-[6-amino-5-(3,4,5-trimethoxyphenyl)pyridin-3-yl]phenol (A3F). Experimental structure, not a prediction.
What the evidence adds up to
A 2013 study using genetically engineered mice with an adult-inducible astrocyte-specific system found that impaired retinoblastoma protein RB tumour suppression produced grade II histopathology. Additional activation of the KRAS network drove progression to grade III disease, and further inactivation of PTEN yielded glioblastoma (GBM). Spontaneous missense mutation of tumour suppressor Trp53 arose after KRAS activation but before grade III progression. The absence of IDH1 mutation, asymptomatic low-grade disease, and rapid emergence of GBM with a mesenchymal transcriptome signature were noted as characteristics of primary GBM. No human survival or response data are reported in this paper.
A 2008 study described mouse models based on conditional inactivation of p53, Nf1, and Pten that developed varying grades of astrocytic malignancy with full penetrance, recapitulating human histology and molecular features. The authors reported a central role for neural stem cells and stem-cell-like cancer cells in tumour initiation and progression. Again, no human clinical outcomes are provided.
A 1987 review of low-grade astrocytomas of childhood stated that astrocytomas are the most frequently encountered brain neoplasms in the paediatric age group. It noted that current management strategies consist of surgery, radiation therapy, chemotherapy and immunotherapy, but that the optimal treatment was yet to be defined. No survival rates, response rates, or sample sizes are given in this abstract.
What is still missing: human clinical trial data for any drug in brain stem astrocytic neoplasms, a defined standard of care for paediatric low-grade astrocytomas, and patient stratification based on the genetic progression events described in the mouse models. Funding for translational studies that move from these murine findings into human trials is also lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 2013 · 56 citations · open access
Evolutionary etiology of high-grade astrocytomas
AbstractGlioblastoma (GBM), the most common brain malignancy, remains fatal with no effective treatment. Analyses of common aberrations in GBM suggest major regulatory pathways associated with disease etiology. However, 90% of GBMs are diagnosed at an advanced stage (primary GBMs), providing no access to early disease stages for assessing disease progression events. As such, both understanding of disease mechanisms and the development of biomarkers and therapeutics for effective disease management are limited. Here, we describe an adult-inducible astrocyte-specific system in genetically engineered mice that queries causation in disease evolution of regulatory networks perturbed in human GBM. Events yielding disease, both engineered and spontaneous, indicate ordered grade-specific perturbations that yield high-grade astrocytomas (anaplastic astrocytomas and GBMs). Impaired retinoblastoma protein RB tumor suppression yields grade II histopathology. Additional activation of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) network drives progression to grade III disease, and further inactivation of phosphatase and tensin homolog (PTEN) yields GBM. Spontaneous missense mutation of tumor suppressor Trp53 arises subsequent to KRAS activation, but before grade III progression. The stochastic appearance of mutations identical to those observed in humans, particularly the same spectrum of p53 amino acid changes, supports the validity of engineered lesions and the ensuing interpretations of etiology. Absence of isocitrate dehydrogenase 1 (IDH1) mutation, asymptomatic low grade disease, and rapid emergence of GBM combined with a mesenchymal transcriptome signature reflect characteristics of primary GBM and provide insight into causal relationships.
Cold Spring Harbor Symposia on Quantitative Biology · 2008 · 32 citations · open access
Neural and Cancer Stem Cells in Tumor Suppressor Mouse Models of Malignant Astrocytoma
AbstractMalignant astrocytomas are highly invasive brain tumors that portend poor prognosis and dismal survival. Mouse models that genetically resemble the human malignancy provide insight into the nature and pathogenesis of these cancers. We previously reported tumor suppressor mouse models based on conditional inactivation of human astrocytoma-relevant genes p53, Nf1, and Pten. These mice develop, with full penetrance, varying grades of astrocytic malignancy that recapitulate the human condition histologically and molecularly. Our studies indicate a central role for neural stem cells and stem-cell-like cancer cells in tumor initiation and progression. These mouse models thus represent powerful tools for investigating various aspects of tumor development that otherwise cannot be explored in humans. Further studies will provide a better understanding of the biology of these tumors and will hopefully pave the way for more effective therapeutic approaches for these devastating diseases.
Current Management of Low-Grade Astrocytomas of Childhood
AbstractAstrocytomas are the most frequently encountered brain neoplasms in the pediatric age group. Current management strategies consist of surgery, radiation therapy, chemotherapy and immunotherapy, although the optimal treatment is yet to be defined. It is hoped that new treatment modalities, and reassessment of current regimens will improve outcome, better in terms of survival and quality of life.
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.
