DeCure for Embryonal carcinoma of the central nervous system
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for embryonal carcinoma of the central nervous system — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEmbryonal carcinoma of the central nervous system maps to a 2-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
approvedDasatinibApproved drug
Structures already discussed alongside embryonal carcinoma of the central nervous system in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Crystal structure of EphA4 kinase domain — Dasatinib has a real, experimentally solved structure in complex with this target (PDB 2Y6O, 1.543 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet 1n1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2Y6O · 1.543 Å · ligand Dasatinib (1N1). Experimental structure, not a prediction.
What the evidence adds up to
In a series of 139 patients with disseminated germinal neoplasms treated between 1973 and 1978, 21 (15.1%) developed brain metastases at some point. Central nervous system spread occurred somewhat more frequently in choriocarcinoma and yolk sac histologies, but all types were at risk. The authors noted that CNS spread almost always occurred in patients with systemic relapse and therefore did not affect overall survival; they had not identified a subgroup that could benefit from prophylactic CNS therapy.
A retrospective review from 2008 to 2010 examined dasatinib, a c-KIT inhibitor, in six patients with central nervous system germ cell tumours — three with newly diagnosed germinoma and three with recurrent disease. The daily dose was 100–170 mg/m², with mostly grade 1–2 toxicities. The authors stated dasatinib may play a role in future treatment strategies for CNS GCT, but the report did not provide response rates or survival data for these six patients.
A separate retrospective study of 24 patients with embryonal CNS tumours treated with an original chemoradiation protocol reported 5-year progression-free survival of 71.1% and overall survival of 88.9% in the average-risk group (n=9), and 66.7% and 71.1% in the high-risk group (n=15). These differences were not statistically significant. Among four patients with supratentorial primitive neuroectodermal tumor, three were disease free. The median follow-up was 73.5 months. Late toxicities included a significant decrease in height standard deviation score (median −1.6 at last assessment) and a median full-scale intelligence quotient of 86. Craniospinal irradiation dose and age at radiation did not influence outcomes or these toxicities.
The 2021 WHO classification update for CNS embryonal tumours is described as providing treatment guidance and prognostic stratification based on histology and molecular genetics, but the abstract offers no specific survival or response data for embryonal carcinoma. What remains missing are prospective trials specifically for embryonal carcinoma of the CNS, adequate sample sizes to stratify by molecular subtype, and funding to move beyond retrospective case series.
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 · 1979 · 59 citations · open access
Brain metastases in disseminated germinal neoplasms. Incidence and clinical course
AbstractFrom July 1973, to March 1978, 139 patients with disseminated germinal neoplasms were treated with a variety of combination chemotherapy regimens. Twenty-one patients (15.1%) exhibited evidence of brain metastases at some time during their course. Central nervous system spread occurred somewhat more frequently in patients with choriocarcinoma and yolk sac histologies, although all types were at risk. This was a major cause of morbidity and mortality. However, central nervous system spread almost always occurred in patients with systemic relapse and thus did not affect overall survival. We have yet to identify a subgroup who potentially could benefit from prophylactic central nervous system therapy.
AbstractThe histological classification of brain tumors currently is based on the morphological appearance and protein expression patterns that reflect specific cell types within the central nervous system. Recent studies have suggested that the cells of origin for brain tumors may persist in the fully formed tumors, and that these "cancer stem cells" might represent the relevant cellular targets for anticancer therapy. In this regard, insights into the developmental neurobiology of brain tumors has significant impact on our understanding of the molecular and cellular pathogenesis of these devastating cancers, as well as the development of new strategies for treating brain tumors.
Feasibility of dasatinib in children and adolescents with new or recurrent central nervous system germinoma
AbstractGerminomas and embryonal carcinomas are central nervous system (CNS) germ cell tumors (GCT) that may overexpress the proto-oncogene c-KIT, a receptor tyrosine kinase, of which dasatinib is a potent inhibitor. This retrospective review presents the feasibility and tolerability of dasatinib administration in select patients with CNS germinoma. Between November 2008 and April 2010, six patients with newly diagnosed (n = 3) or recurrent (n = 3) CNS GCT were treated in an effort to avoid irradiation and/or delay recurrence. The daily doses administered were 100-170 mg/m(2) with mostly grade 1-2 toxicities. Dasatinib may play a role in future treatment strategies for CNS GCT.
Radiation Oncology · 2014 · 13 citations · open access
Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors
AbstractBACKGROUND: Standard treatment strategies for embryonal central nervous system (CNS) tumors have not yet been established. We treated these tumors using an original chemoradiation therapy protocol; the clinical outcomes and toxicities were retrospectively evaluated. METHODS: Twenty-four patients were enrolled including sixteen with medulloblastoma, four with supratentorial primitive neuroectodermal tumor (sPNET), three with atypical teratoid/rhabdoid tumor, and one with pineoblastoma. Immediately after diagnosis, all patients underwent surgery initially. They were then categorized as high- or average-risk groups independent of tumor type/pathogenesis. The average-risk group included patients who were aged ≥3 years at diagnosis, had non-metastatic disease at diagnosis (M0), and had undergone gross total resection. Other patients were categorized as the high-risk group; this group received more intensive treatment than the average-risk group, including high-dose chemotherapy with autologous stem-cell transplantation. All patients received craniospinal irradiation (CSI). The CSI dose was 23.4 Gy for M0 patients aged ≥5 years, 18 Gy for M0 patients aged <5 years, and 30-36 Gy for all patients with M + disease. The total dose to the primary tumor bed was 54 Gy. RESULTS: The median follow-up time was 73.5 (range, 19-118) months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 71.1 and 88.9%, respectively in the average-risk group (n = 9) and 66.7 and 71.1%, respectively in the high-risk group (n = 15). The PFS and OS rates were not significantly different between the average- and high-risk groups. In patients with medulloblastoma only, these rates were also not significantly different between the average- and high-risk groups. Three of four patients with sPNET were disease free. The height standard deviation score (SDS) was significantly decreased at the last assessment relative to that at diagnosis (P < 0.0001). The latest median height SDS was -1.6 (range, 0.9 to -4.8), and the latest median full-scale intelligence quotient (FSIQ) score was 86 (range, 59-128). The CSI doses and age at the start of radiation therapy did not influence clinical outcomes, height SDSs, and FSIQ scores. CONCLUSIONS: Our original protocol for patients with embryonal CNS tumors was feasible and yielded favorable clinical outcomes.
DOAJ (DOAJ: Directory of Open Access Journals) · 2021 · 0 citations · open access
Interpretation on embryonal tumors in the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition)
AbstractEmbryonal tumors of central nervous system (CNS) are a class of highly heterogeneous brain tumors and the most common malignant brain tumors in children. Researches based on histology and molecular genetics can classify them. This kind of researches only can not stratify the prognosis of embryonic tumors, but also provide treatment guidance for them. The 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition) updated the classification of embryonal tumors. This article will interpret the updating from two aspects of medulloblastoma and other CNS embryonal tumors.
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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