DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for astroblastoma, MN1-altered — 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 moduleAstroblastoma, MN1-altered 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
No approved-drug candidate for astroblastoma, mn1-altered 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
ATM serine/threonine kinase (ATM) — ATM 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 anpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8OXQ · 2.5 Å · ligand PHOSPHOAMINOPHOSPHONIC ACID-ADENYLATE ESTER (ANP). Experimental structure, not a prediction.
What the evidence adds up to
Astroblastoma is a rare glioma whose diagnosis rests on histologic findings of astroblastomatous pseudorosettes and vascular hyalinisation, but molecular analysis of eight cases found that this histology is not specific to any single entity. Four of those eight cases showed MN1 alteration by FISH; two were paediatric cases lacking other pathogenic alterations, while two adult cases harboured additional mutations such as CDKN2A/B homozygous deletion, TP53, ATM and TERT promoter mutations. Three of the four MN1-altered cases clustered with the CNS-HGNET-MN1 group by methylation profiling. Among the four MN1-intact cases, two showed genetic features of anaplastic pleomorphic xanthoastrocytoma or IDH-wildtype glioblastoma and had an aggressive clinical course; two clinically indolent cases remained unclassifiable despite multimodal analysis. The authors concluded that astroblastoma histology is not specific and that additional genetic characterisation should be considered, as many such tumours likely belong to other entities.
A separate case of a 9-year-old girl with high-grade astroblastoma was reported in 2014, with gross total resection achieved; the authors noted that recurrence is high and that the roles of radiotherapy and chemotherapy remain unclear. In 2018, a case of a 6-year-old girl with a pathognomonic MN1:BEND2 fusion was studied over ten years and eleven surgical interventions. Phylogenetic reconstruction showed that initial treatment drove tumour dissemination along four distinct trajectories, with infiltration of distant sites associated with gains of chromosomal arms and later genome doubling. Convergent evolution of different lesions acquired distinct alterations targeting the NF-kB pathway, supported by strong immunohistochemical staining of RELA and high expression of target genes such as IL8.
In 2021, a paediatric astroblastoma case with a novel MN1-GTSE1 fusion and a concurrent EWSR1-PATZ1 fusion was reported. Methylation analysis was uninformative and did not cluster with known CNS-HGNET-MN1 cases; whole genome sequencing was required to confirm the diagnosis. A 2025 case report described a 4-year-old girl with CNS WHO Grade 3 MN1-altered astroblastoma who also carried a heterozygous BRCA2 mutation. After maximal safe resection, she received proton beam therapy (craniospinal 36 Gy, local boost 54 Gy). Residual tumour persisted, and the PARP inhibitor fluzoparib was given, associated with temporary disease stabilisation. After a second resection, salvage Gamma Knife radiosurgery (30 Gy in 5 fractions) was administered, and the patient showed sustained local control with no progression for over 18 months, with only mild asymptomatic perilesional oedema.
What is still missing are prospective trials that could establish standard treatment protocols for this rare tumour. The molecular heterogeneity — with some cases carrying MN1 fusions, others harbouring BRAF V600E, IDH-wildtype glioblastoma signatures, or concurrent fusions like EWSR1-PATZ1 — means that patient stratification by genomic and methylation profiling is essential but not yet routine. The roles of radiotherapy, chemotherapy, and targeted agents such as PARP inhibitors remain anecdotal, and no controlled data exist to guide their use. Funding for multi-centre molecular registries and preclinical models of MN1-altered tumours is 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.
Brain Pathology · 2017 · 118 citations · open access
Multimodal molecular analysis of astroblastoma enables reclassification of most cases into more specific molecular entities
AbstractAstroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1). To further characterize the genetic alterations that drive astroblastomas, we performed targeted next-generation sequencing (NGS) of 500 cancer-associated genes in a series of eight cases. We correlated these findings with break-apart fluorescence in situ hybridization (FISH) analysis of the MN1 locus and genome-wide DNA methylation profiling. Four cases showed MN1 alteration by FISH, including two pediatric cases that lacked other pathogenic alterations, and two adult cases that harbored other cancer-associated gene mutations or copy number alterations (eg, CDKN2A/B homozygous deletion, TP53, ATM and TERT promoter mutations). Three of these cases grouped with the CNS-HGNET-MN1 entity by methylation profiling. Two of four MN1 intact cases by FISH showed genetic features of either anaplastic pleomorphic xanthoastrocytoma (BRAF p.V600E mutation, CDKN2A/B homozygous deletion and TERT promoter mutation) or IDH-wildtype glioblastoma (trisomy 7, monosomy 10, CDK4 amplification and TP53, NRAS and TERT promoter mutations) and these cases had an aggressive clinical course. Two clinically indolent cases remained unclassifiable despite multimodal molecular analysis. We conclude that astroblastoma histology is not specific for any entity including CNS-HGNET-MN1, and that additional genetic characterization should be considered for astroblastomas, as a number of these tumors likely contain a methylation profile or genetic alterations that suggest classification as other tumor entities. Our heterogeneous molecular findings help to explain the clinical unpredictability of astroblastoma.
Neuropathology and Applied Neurobiology · 2021 · 18 citations · open access
A rare case of paediatric astroblastoma with concomitant <i>MN1</i>‐<i>GTSE1</i> and <i>EWSR1</i>‐<i>PATZ1</i> gene fusions altering management
AbstractIn a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS-HGNET-MN1 cases. Whole genome sequencing however identified a novel MN1-GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1-PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours.
Surgical Neurology International · 2014 · 17 citations · open access
High-grade astroblastoma in a child: Report of one case and review of literature
AbstractBACKGROUND: Astroblastoma is a rare glial neoplastic lesion that affects children and adolescents; its histogenesis remains uncertain. It is considered to account for 0.5% of all glial neoplasms, and two different subtypes have been defined based upon histologic characteristics. CASE DESCRIPTION: We present the case of a 9-year-old girl who presented with headache, motor symptoms, and seizures few days before she was admitted to our institution. Computed tomography (CT) and magnetic resonance imaging (MRI) scans showed an intra-axial heterogeneous frontoparietal lesion with a striking "bubbly" appearance in MRI T2-weighted sequences and features of intracranial hypertension. Gross total resection of the tumor was achieved and the histopathologic diagnosis revealed high-grade astroblastoma. We reviewed the current published cases of astroblastoma to highlight the demographic, clinical, radiologic, and pathologic data. CONCLUSION: Astroblastomas are a distinct clinicopathologic entity, with well-described radiologic, pathologic, and cytogenetic features. Its recurrence is high and efforts must be made to elucidate the role and usefulness of radiotherapy and chemotherapy in these tumors.
CRAN-20. THE TEN-YEAR EVOLUTIONARY TRAJECTORY OF A HIGHLY RECURRENT PAEDIATRIC HIGH GRADE NEUROEPITHELIAL TUMOUR WITH MN1:BEND2 FUSION
AbstractAstroblastomas are rare brain tumours which predominate in children and young adults, and have a controversial claim as a distinct entity, with no established WHO grade. Reports suggest a better outcome than high grade gliomas, though they frequently recur. Recently, they have been described to overlap with a newly-discovered group of tumours described as ‘high grade neuroepithelial tumour with MN1 alteration’ (CNS HGNET-MN1), defined by global methylation patterns and strongly associated with gene fusions targeting MN1. We have studied a rare case of astroblastoma arising in a 6 year-old girl, with multiple recurrences over a period of 10 years, with the pathognomonic MN1:BEND2 fusion. Exome sequencing of eleven surgical interventions allowed for a phylogenetic reconstruction of tumour evolution, which when integrated with clinical, pathological and radiological data provide for a detailed understanding of disease progression, with initial treatment driving tumour dissemination along four distinct trajectories. Infiltration of distant sites was associated with gains of chromosomal arms and later genome doubling. There was evidence of convergent evolution of different lesions acquiring distinct alterations targeting the NF-kB pathway, supported by strong immunohistochemical staining of RELA, and high levels of target gene expression, such as IL8. These data represent an unique opportunity to understand the evolutionary history of a highly recurrent childhood brain tumour, and provide novel therapeutic targets for astroblastoma / CNS HGNET-MN1.
Frontiers in Oncology · 2025 · 1 citations · open access
Case Report: Multimodal management of a rare pediatric astroblastoma using proton beam therapy and Gamma Knife radiosurgery—a case report and literature review
AbstractIntroduction: Astroblastoma is an infrequent glial tumor, with the MN1-altered subtype recognized in the 2021 WHO classification. This report details the management of a 4-year-old girl diagnosed with CNS WHO Grade 3 MN1-altered astroblastoma, also found to have a heterozygous BRCA2 mutation. We highlight a sequential multimodal treatment approach involving proton beam therapy (PBT), targeted chemotherapy with a PARP inhibitor, and subsequent salvage Gamma Knife radiosurgery (GKRS). Main symptoms and findings: The patient presented with right lower extremity weakness and gait disturbance. Initial treatment involved maximal safe resection followed by adjuvant PBT (craniospinal irradiation 36 Gy, local boost to 54 Gy). PBT was selected for its dosimetric advantages, notably minimizing radiation dose to surrounding healthy tissues, thereby reducing potential acute toxicity and long-term risks compared to conventional photon therapy. Despite this, residual tumor persisted. Following the discovery of a BRCA2 mutation, the PARP inhibitor fluzoparib was administered, which was associated with temporary disease stabilization. Diagnoses interventions outcomes: After a second resection confirming residual disease, salvage stereotactic radiosurgery (SRS) using Gamma Knife (30 Gy in 5 fractions) was administered to the remaining lesions. The patient has demonstrated sustained local control with no tumor progression for over 18 months post-SRS, with only mild, asymptomatic perilesional edema and no neurological deficits. Conclusion - Take-away lesson: This case suggests that leveraging the tissue-sparing benefits of initial PBT may enable effective salvage SRS for managing residual or recurrent high-grade pediatric astroblastoma. Furthermore, it highlights the potential role of molecular profiling to guide targeted therapies in these rare tumors.
Apollo (University of Cambridge) · 2021 · 0 citations · open access
A rare case of paediatric astroblastoma with concomitant MN1-GTSE1 and EWSR1-PATZ1 gene fusions altering management.
AbstractIn a case of astroblastoma, methylation analysis was uninformative, with no clustering with known CNS-HGNET-MN1 cases. Whole genome sequencing however identified a novel MN1-GTSE1 gene fusion (image), confirming the diagnosis of astroblastoma, as well as an EWSR1-PATZ1 gene fusion. Whole genome sequencing, alongside methylation profiling and conventional neuropathology, will continue to lead to improved diagnostics and prognostication for children with brain tumours.
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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