DeCure for High-grade astrocytoma with piloid features
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for high-grade astrocytoma with piloid features — 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 moduleHigh-grade astrocytoma with piloid features 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 high-grade astrocytoma with piloid features 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
dicer 1, ribonuclease III (DICER1) — DICER1 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 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
A 2016 analysis of 98 cases with histological features of anaplastic pilocytic astrocytoma identified a distinct methylation cluster of 73 tumours. Median age in that group was 43 years; only 6 of 69 cases (9%) were paediatric. 56 of 67 (84%) were located in the cerebellum. The most frequent molecular alterations were deletions of CDKN2A/B (64 of 73, 87%), alterations of the MAPK pathway (19 of 24, 79%, mostly NF1 mutations and BRAF fusions), and loss of ATRX (31 of 69, 45%). Outcome was aggressive: 12 of 28 patients (43%) had died, with a median survival of 13 months. A 2019 case report of a radiation-naive patient with pilocytic astrocytoma noted that deletions of CDKN2A and PTEN portended poor clinical outcome, and the authors called for comprehensive genomics in larger series of adult pilocytic astrocytoma.
A 2021 retrospective review of 73 paediatric glial tumours (53 astrocytomas) reported a 5-year overall survival of 40% for astrocytoma overall, and 77.2% for grade I, 45% for grade II, 32% for grade III, and 0% for grade IV. The 5-year survival for supratentorial tumours was 25.6%, for infratentorial 63.6%, and for spinal 50%. Cox regression showed tumour resection and grade affected prognosis. The authors stated treatment results are not satisfactory in high-grade astrocytomas and called for new approaches that incorporate molecular features.
A 2004 review noted that conventional surgery, radiotherapy and chemotherapy have failed to significantly improve prognosis in malignant astrocytomas, and that therapeutic efficacy will likely require combinatorial therapy with small incremental efficacy in selected subgroups. A 1989 report described a single case of recurrent grade III astrocytoma in a 36-year-old woman treated with re-irradiation and chemotherapy, but gave no survival or response data beyond noting that re-irradiation had produced only occasional short remissions in previous reports. A 1998 cytodiagnostic study of 23 pilocytic astrocytomas described smear features and stated that mitoses and necrosis were absent, but did not address treatment or survival.
What is still missing: prospective trials that stratify anaplastic pilocytic astrocytoma by CDKN2A/B, MAPK pathway, and ATRX status; adequate sample sizes for adult and paediatric subgroups; and funding for molecularly guided, combinatorial therapy studies rather than single-agent repurposing attempts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Neurology · 2004 · 47 citations
Advances in the biology of astrocytomas
AbstractPURPOSE OF REVIEW: Conventional surgery, radio- and chemotherapy have failed to significantly improve the prognosis of patients with malignant astrocytomas--hence the need for understanding their molecular biology. Harvesting this understanding to yield novel biological targeted therapies has approached the clinical doorstep. Therapeutic efficacy will likely require combinatorial therapy involving biologicals and conventional therapies, with small incremental efficacy in selected sub-groups. This review highlights some of the findings over the past year (June 2003-2004) that have contributed to this slow but essential journey towards our understanding of the biology of astrocytomas. RECENT FINDINGS: The accumulation of loss and/or gain of function molecular alterations underlying astrocytoma formation, progression and key growth parameters including proliferation, angiogenesis, apoptosis, invasion and resistance are emerging. These alterations involve those regulating the growth factor/receptor and downstream signaling networks, cell cycle, immune modulators and other key biological processes. The advances are facilitated by interactions amongst clinician and basic scientists, in both academia and industry. They have incorporated high-throughput bioinformatics analysis of genomic and expression array data, the emerging field of proteomics and development of various genetically engineered models of astrocytomas. SUMMARY: Astrocytomas, like other cancers, are a result of several molecular alterations, some of which strongly correlate to their pathological grade. However, molecular heterogeneity exists between astrocytomas of similar grades and likely between varying micro-environmental regions of a single tumor. Characterization of the molecular signature of an astrocytoma and linking with the appropriate 'tailored' therapie(s) is the hope of the future.
Cytodiagnosis of Pilocytic Astrocytoma in Smear Preparations
AbstractOBJECTIVE: To assess the cytologic features in smear preparations of 23 pilocytic astrocytomas. STUDY DESIGN: Examination of 23 smears. RESULTS: In all cases, the diagnosis was subsequently confirmed on histologic sections. The smears were moderately cellular, with a variably myxoid background. They showed bipolar "hair" cells with elongated, coarse cytoplasmic processes; bland, oval nuclei; Rosenthal fibers; eosinophilic granular bodies; and hyalinized vessels. Stellate cells and bare tumor nuclei were also present. Nuclear pleomorphism, vascular proliferation, perivascular pseudorosettes, microcalcification and hemosiderin-laden macrophages were infrequent features. Mitoses and necrosis were absent. The differential diagnosis should include diffuse fibrillary astrocytomas of all histologic grades, pleomorphic xanthoastrocytoma, ganglion cell tumor, ependymoma and reactive gliosis. CONCLUSION: Correlation of cytologic features with clinical and radiologic information allows pilocytic astrocytoma to be distinguished from other conditions.
AbstractAstrocytoma of the brain in adults is invariably a fatal disease. The majority of cases present with inoperable, high-grade III or IV tumours. The place of radiotherapy in the management of such cases is of limited value. However, prolonged remission, and even occasional cures, have been reported (Sheline, 1977). Recurrence of high-grade astrocytoma long after surgery and/or radiotherapy is a rare event in clinical practice. Radical surgery has no place in such cases. Chemotherapy has also been tried with occasional transient success (Levin et al, 1980). Re-irradiation of selected cases has been tried in the past with occasional short remission in some patients (Dritschillo et al, 1981). We present the treatment result of a 36-year-old woman with recurrent Grade III astrocytoma, 9 years after initial biopsy and radiotherapy, who was given a second course of radiotherapy and chemotherapy.
Clinical Importance of CDKN2A Loss and Monosomy 10 in Pilocytic Astrocytoma
AbstractThis case of a radiation-naive patient with pilocytic astrocytoma highlights how deletions of CDKN2A (cyclin-dependent kinase Inhibitor 2A) and PTEN (phosphatase and tensin homolog) portended a poor clinical outcome. Pilocytic astrocytomas are grade 1 tumors usually occurring in children and young adults with KIAA1549-BRAF fusion defining the majority of pilocytic astrocytomas. The presence of CDKN2A and PTEN loss may be associated with aggressive biology in pilocytic astrocytoma and further studies should include comprehensive genomics in a larger series of adult pilocytic astrocytoma to evaluate this previously unreported finding. Providers need to be aware of this possibility given the potential for poor outcomes.
Turkish Neurosurgery · 2021 · 0 citations · open access
Clinical features, treatment, and outcome of childhood glial tumors
AbstractAIM: To evaluate the clinical features, treatment approaches, and outcomes of glial tumors in children. MATERIAL AND METHODS: Files (2006 to 2020) of children diagnosed with glial tumors and followed-up were reviewed retrospectively. Information regarding demographic and clinical characteristics, treatment approaches, and outcomes were retrieved from the patients? files. RESULTS: Of the total of 180 pediatric patients diagnosed with brain tumors, 73 (40.6%) had glial tumors. The children with astrocytoma were in the age range of 2?18 years (median age: 8.7 years), while the ages of children with ependymoma ranged from three months to 10 years (median age: 3 years). This difference was statistically significant (p < 0.0001). The male to female ratio was 1.6. The most common symptoms or signs were headaches (n=34, 46.6%), abnormal gait or coordination (n=22, 30.2%), vomiting (n=21, 28.8%), and cranial nerve palsies (n=20, 27.4%). The pathological diagnoses were astrocytomas (n=53, 72.6%), oligodendroglial tumors (n=2, 2.7%), ependymoma (n=15, 20.7%), and other glial tumors (n=3, 4.1%). The most common tumor location was supratentorial (n=42, 57.5%), while midline glioma was detected in seven patients. The 5-year overall survival (OS) rate of all glial tumors, astrocytoma, and ependymoma was 42%, 40%, and 55%, respectively. The 5-year OS rate of the tumor Grade I, II, III, and IV was 77.2%, 45%, 32%, and 0%, respectively (p < 0.0001). The 5-year OS rate of supratentorial, infratentorial, and spinal tumors was 25.6%, 63.6%, and 50%, respectively (p=0.021). In Cox regression analysis, it was found that the tumor resection and grade had an effect on the tumor prognosis. CONCLUSION: Treatment results are not satisfactory in high-grade astrocytomas. There is a need for new treatment approaches that would take cognizance of molecular features and adopt multidisciplinary approaches.
HG-68COMBINED ALTERATIONS IN MAPK PATHWAY GENES, CDKN2A/B AND ATRX CHARACTERIZE ANAPLASTIC PILOCYTIC ASTROCYTOMA
AbstractTumors with histological features of pilocytic astrocytoma but with increased mitotic activity and additional high grade features (i.e. microvascular proliferation, necrosis) have been designated anaplastic pilocytic astrocytomas (APA). Patients with such tumors are thought to have an unfavorable clinical outcome. The status of APA as a separate entity has not yet been established and molecular features have only partially been elucidated. We analyzed a large retrospective series of 98 cases with histological features of APA by genome wide DNA methylation profiling, copy number analysis, targeted sequencing and, in a subset, panel sequencing. Unsupervised hierarchical clustering analysis of 450k methylation data together with over 250 reference cases of 13 established glioma classes (glioblastoma, astrocytoma, oligodendroglioma, pleomorphic xanthoastrocytoma, pilocytic astrocytoma, ganglioglioma, dysembryoplastic neuroepithelial tumor and diffuse leptomeningeal glioneuronal tumor) allowed the identification of a distinct methylation cluster comprising 73 APA (“APA core group”). Most of the remaining cases clustered into other tumor classes. The median age of the APA core group was 43 years with only 6/69 (9%) of cases occurring in pediatric patients; 56/67 (84%) were located in the cerebellum. The most frequent molecular alterations were deletions of CDKN2A/B (64/73, 87%) followed by alterations of the MAPK pathway (19/24, 79%, mostly NF1 mutations and BRAF fusions) and loss of ATRX (31/69, 45%). Outcome analysis confirmed an aggressive course with 12/28 (43%) patients deceased (median survival 13 months). In summary, APA is characterized by increased patient age, predominant cerebellar location, frequent MAPK pathway alterations, CDKN2A/B deletion, ATRX loss and unfavorable prognosis.
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.
