DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for pleomorphic xanthoastrocytoma — screening already-approved drugs against its 17-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePleomorphic xanthoastrocytoma maps to a 17-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 pleomorphic xanthoastrocytoma 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
platelet derived growth factor receptor alpha (PDGFRA) — PDGFRA 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 dimethylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5GRN · 1.77 Å · ligand N-[2-(dimethylamino)ethyl]-N-[[4-[[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]carbamoyl]phenyl]methyl]pyridine-3-carboxamide (748). Experimental structure, not a prediction.
What the evidence adds up to
Pleomorphic xanthoastrocytoma is a rare primary CNS tumour. A 2023 single-centre study of 26 high-grade PXA patients (mean age 36.7 years) reported that after a mean follow-up of 20.5 months, 7 patients had recurrence and 6 had died, with a mean overall survival time of 19.4 months. In a pooled literature analysis of 56 additional high-grade PXA cases, the mortality rate was 32.5% and the recurrence rate was 70% after a median follow-up of 31.4 months. The same study found that gross-total resection was achieved in 65.4% of the institutional cohort and 44.4% of the literature cases. Non-gross-total resection, age 30 or older, no radiotherapy, and no chemotherapy were all negative prognostic factors for progression-free survival; the same factors plus secondary (rather than primary) high-grade PXA were risk factors for worse overall survival.
BRAF mutations are present in a substantial percentage of PXA, and a 2023 study reported a BRAF mutation frequency of 47.5% in high-grade PXA. However, that study found no connection between BRAF mutations and clinical outcomes. A 2019 review noted that the discovery of BRAF mutations has fostered a clearer understanding of PXA pathophysiology and has prognostic and therapeutic implications, but did not report specific survival or response data for any BRAF-targeted therapy.
Earlier case reports describe long survival: one patient from 1966 was alive and symptom-free 18 years after surgery, and a 1987 report described a typical PXA in a 62-year-old man, noting that tumours closely resembling PXA can behave aggressively. The 2023 study concluded that children and younger adults have better outcomes than older patients, and that complete surgical excision plus radiotherapy and chemotherapy is recommended for high-grade PXA. What remains missing are prospective trials with larger, stratified cohorts, standardised treatment protocols, and data on whether BRAF-directed therapies improve outcomes in the high-grade subgroup.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
CNS Oncology · 2019 · 103 citations · open access
Pleomorphic xanthoastrocytoma: a brief review
AbstractPleomorphic xanthoastrocytoma (PXA) is a rare primary CNS tumor. Recent advances in the molecular characterization are helping to define subtypes of tumor. The discovery of BRAF mutations within a substantial percentage of PXA fosters a clearer understanding of the pathophysiology of these tumors with clear prognostic and therapeutic implications. These findings are expected to provide insight into the spectrum of clinical behavior observed in PXA, ranging from cure with surgery to diffuse dissemination throughout the neuraxis. This review details the clinical presentation including radiographic appearance of PXA. Pathology, including molecular pathology is discussed. Therapeutic management including surgical resection, radiotherapy and systemic therapies are reviewed.
Pleomorphic xanthoastrocytoma with 18-year survival
AbstractThe authors present a case of right parietal pleomorphic xanthoastrocytoma that occurred in a 24-year-old man. The patient was originally operated on in 1966, and at that time the diagnosis of monstrocellular sarcoma was made. The patient is still alive and totally symptom-free. A careful reevaluation of the microscopic findings, including positive glial fibrillary acidic protein staining, led to the definite diagnosis of pleomorphic xanthoastrocytoma.
Neuropathology and Applied Neurobiology · 1987 · 42 citations
PLEOMORPHIC XANTHOASTROCYTOMA IN A 62‐YEAR‐OLD MALE
AbstractPleomorphic xanthoastrocytoma has been described as a distinct clinicopathological entity with a relatively favourable prognosis. However, tumours closely resembling this entity have been shown to have the potential for aggressive behaviour, and to represent, on closer scrutiny, a number of disparate neoplasms. A case is described which, although otherwise typical of pleomorphic xanthoastrocytoma, occurred in a man of 62 years, and it is suggested that it should be considered a specific histological, rather than a clinicopathological entity.
Frontiers in Oncology · 2023 · 3 citations · open access
Clinical features and surgical outcomes of high grade pleomorphic xanthoastrocytomas: a single-center experience with a systematic review
AbstractPurpose: High grade pleomorphic xanthoastrocytomas (HGPXAs) are very rare and their management and prognostic outcomes remain unclear. To better understand the disease, we aimed to evaluate the risk factors for progression-free survival (PFS) and overall survival (OS), and propose a treatment protocol based on cases from our institute and cases from the literature. Methods: The authors reviewed the clinical data of 26 patients with HGPXAs who underwent surgical treatment in Department of Neurosurgery of Beijing Tiantan Hospital between August 2014 and September 2021. We also searched the PubMed database using the keywords "anaplastic" combined with "pleomorphic xanthoastrocytoma(s)" between January 1997 and October 2022. Risk factors for PFS and OS were evaluated in the pooled cases. Results: The authors' cohort included 11 males and 15 females with a mean age of 36.7 ± 20.3 years (range: 5.5-71 years). Gross-total resection (GTR) and non-GTR were achieved in 17 (65.4%) and 9 (34.6%) patients, respectively. Radiotherapy and chemotherapy were administered to 22 and 20 patients, respectively. After a mean follow-up of 20.5 ± 21.2 months (range: 0.5-78.1 months), 7 patients suffered tumor recurrence and 6 patients died with a mean OS time of 19.4 ± 10.8 months (range: 8-36 months). In the literature between January 1997 and October 2022, 56 cases of HGPXAs were identified in 29 males and 27 females with a mean age of 29.6 ± 19.6 years (range; 4-74 years). Among them, 24 (44.4%) patients achieved GTR. Radiotherapy and chemotherapy was administered to 31 (62%) patients and 23 (46%) patients, respectively. After a median follow-up of 31.4 ± 35.3 months (range: 0.75-144 months), the mortality and recurrence rates were 32.5% (13/40) and 70% (28/40), respectively. Multivariate Cox regression model demonstrated that non-GTR (HR 0.380, 95% CI 0.174-0.831, p=0.015), age≥30 (HR 2.620, 95% CI 1.183-5.804, p=0.018), no RT (HR 0.334,95% CI 0.150-0.744, p=0.007) and no CT (HR 0.422, 95% CI 0.184-0.967, p=0.042) were negative prognostic factors for PFS. Non-GTR (HR 0.126, 95% CI 0.037-0.422, p=0.001), secondary HGPXAs (HR 7.567, 95% CI 2.221-25.781, p=0.001), age≥30 (HR 3.568, 95% CI 1.190-10.694, p=0.023) and no RT (HR 0.223,95% CI 0.073-0.681, p=0.008) were risk factors for OS. Conclusion: High grade pleomorphic xanthoastrocytomas are very rare brain tumors. Children and younger adults have better clinical outcome than elderly patients. Secondary HGPXAs had worse OS than primary HGPXAs. Complete surgical excision plus RT and CT is recommended for this entity. The frequency of BRAF mutations in HGPXAs is 47.5% (19/40) in this study, however, we do not find the connections between BRAF mutations and clinical outcomes. Future studies with larger cohorts are necessary to verify our findings.
Neurosurgery Cases and Reviews · 2020 · 0 citations · open access
Pleomorphic Xanthoastrocytoma Presenting as Long-Term Complex Focal Epilepsy of the Frontal Lobe: Case Report
AbstractPleomorphic xanthoastrocytoma (PXA) is a rare tumor with favorable prognosis, classified as grade II in the World Health Organization (WHO) and accounts for less than 1% of all astrocytic neoplasm. It is commonly found in childhood and young adults. This tumor has been described as part of the spectrum of Long-Term Epilepsy Associated Tumors (LEAT). The most common location is supratentorial, involving predominantly the temporal lobe.
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.
