DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for primitive neuroectodermal tumor — 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 modulePrimitive neuroectodermal tumor 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 primitive neuroectodermal tumor 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
isocitrate dehydrogenase (NADP(+)) 2 (IDH2) — IDH2 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I96 · 1.55 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Betulinic acid induced apoptosis in neuroectodermal tumour cells (neuroblastoma, medulloblastoma, glioblastoma, Ewing sarcoma) by a direct effect on mitochondria, independent of p53 or CD95 systems. Overexpression of Bcl-2 or Bcl-XL blocked this effect. Betulinic acid showed activity against neuroblastoma cells resistant to CD95- or doxorubicin-triggered apoptosis and against primary tumour cells from patients. No human survival data were provided in that study.
A retrospective review of primitive neuroectodermal tumours of the head and neck found that 31% of patients had metastatic disease at diagnosis. Therapy included surgery, chemotherapy, and radiation. Survival was poor, with 65% of patients alive at 2 years. A later series of 36 children with peripheral PNET who received surgery, chemotherapy and radiotherapy reported a response rate of 94.4% at the end of therapy (30 complete remissions, 2 partial remissions). However, 46.7% of those who achieved remission later recurred. Median survival was 29 months. The 1-, 3-, and 5-year overall survival rates were 94.4%, 50.0%, and 30.6%, respectively. Patients with metastasis at diagnosis had a median survival of 10 months versus 33 months for those without metastasis.
Imaging studies of 16 peripheral PNETs described them as large, ill-defined solid masses with aggressive extension, necrosis in 11 of 16 cases, and haemorrhage in 5 of 16. The diagnosis remains difficult; early diagnosis rates are low. What is still missing are prospective trials that stratify patients by metastatic status at diagnosis, standardised chemotherapy regimens tested against current best supportive care, and funding for studies that move beyond retrospective chart review.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Medical and Pediatric Oncology · 2000 · 142 citations
Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors
AbstractBACKGROUND AND PROCEDURE: We identified BetA as a new cytotoxic agent active against neuroectodermal tumor cells including neuroblastoma, medulloblastoma, glioblastoma and Ewing sarcoma cells, representing the most common solid tumors of childhood. RESULTS: BetA induced apoptosis by a direct effect on mitochondria independent of accumulation of wild-type p53 protein and independent of death-inducing ligand/receptor systems such as CD95. Mitochondrial perturbations on treatment with BetA resulted in the release of soluble apoptogenic factors such as cytochrome c or AIF from mitochondria into the cytosol, where they induced activation of caspases. Overexpression of the anti-apoptotic proteins Bcl-2 or Bcl-X(L) that blocked loss of the mitochondrial membrane potential and cytochrome c release from mitochondria also conferred resistance to BetA. Most importantly, BetA exhibited potent antitumor activity on neuroblastoma cells resistant to CD95- or doxorubicin-triggered apoptosis and on primary tumor cells from patients with neuroectodermal tumors. CONCLUSIONS: Thus, BetA may be a promising new agent in the treatment of neuroectodermal tumors including neuroblastoma in vivo.
Archives of Otolaryngology - Head and Neck Surgery · 1995 · 125 citations
Peripheral Primitive Neuroectodermal Tumors of the Head and Neck
AbstractOBJECTIVE: Primitive neuroectodermal tumor is a malignant small round cell tumor of neuroectodermal origin. The occurrence of these tumors in the head and neck is rare. Our objective is to document the frequency of presentation, methods of diagnosis, and forms of treatment used to combat primitive neuroectodermal tumors in the head and neck. DESIGN: Retrospective chart review. RESULTS: The most common location for primitive neuroectodermal tumors in our series was the thoracopulmonary region (46%); the next most common location was the head and neck (42%). Metastatic disease was present in 31% of patients at the time of diagnosis. Cytogenic analysis was found to be helpful in confirming the diagnosis of primitive neuroectodermal tumor. Therapy for primitive neuroectodermal tumors included surgery, chemotherapy, and radiation therapy. Survival statistics were poor, with 65% of the patients alive at 2 years' follow-up. CONCLUSIONS: Primitive neuroectodermal tumor is an aggressive malignant small round cell tumor that may present in the head and neck. Long-term survival for patients with primitive neuroectodermal tumor is still poor; however, the use of improved chemotherapeutic agents combined with aggressive surgical control of primary disease and, in some cases, radiation therapy should lead to improved long-term survival.
Journal of Computer Assisted Tomography · 2016 · 0 citations
Computed Tomography and Magnetic Resonance Imaging Characteristics of Peripheral Primitive Neuroectodermal Tumor
AbstractPURPOSE: The aim of this study was to analyze the radiological features of peripheral primitive neuroectodermal tumor (pPNET). MATERIALS AND METHODS: The radiological and clinical findings for 16 patients with pPNETs were retrospectively reviewed. The 16 tumors were classified into 4 groups (meninges group, n = 4; spine group, n = 3; bone group, n = 5; soft-tissue group, n = 4), and clinical data, size, and common and unique CT/MRI characteristics were assessed. RESULTS: Peripheral primitive neuroectodermal tumors presented as large solid masses with aggressive extension into the neighboring tissue. Most tumors (11/16) presented with necrosis, and 5 of the 16 cases showed signs of hemorrhage. The "dural tail sign" was observed in the meninges and spine groups. The pPNETs of bone demonstrated bony destruction with spiculated periosteal reaction, and small nourishing vessels were found in tumors in the soft-tissue group. CONCLUSIONS: Peripheral primitive neuroectodermal tumor should be suggested as an important differential diagnosis when the tumor presents as a large, ill-defined solid mass with aggressive extension and significant enhancement.
Clinical outcomes of 36 children with peripheral primitive neuroectodermal tumor receiving comprehensive therapy
AbstractObjective: To investigate the clinical features of children with peripheral primitive neuroectodermal tumor (pPNET) and the efficacy of comprehensive therapy in these patients. Methods: The medical records and the follow-up information of 36 children with pPNET were collected and reviewed. All these patients received surgery, chemotherapy and radiotherapy between January 2002 and January 2013 in Tianjin Medical University Cancer Institute and Hospital. The therapeutic effect, recurrence rate and 1-, 3- and 5-year overall survival rates were analyzed. Results: At the end of the comprehensive therapy, 30 cases achieved complete remission, 2 cases achieved partial remission, 2 cases were in stable disease, one case had progressive disease, and one died of pPNET; the response rate reached 94.4%. By the end of the follow up, 14 (46.7%) cases had tumor recurrence; sixteen cases had a disease-free survival, 4 cases survived with tumor, while 12 cases died of recurrence and 4 cases died of tumor progression. The median survival time was 29 months. The 1-, 3- and 5-year overall survival rate of all 36 cases were 94.4%, 50.0% and 30.6%, respectively. The median survival time of cases who were initialy diagnosed of metastatic pPNET was poorer than that of the cases who were initialy diagnosed of pPNET without metastasis (10 months vs 33 months, P = 0.001). Conclusion: Children with pPNET have very poor prognosis. Those who are initialy diagnosed of pPNET without metastasis have a better clinical outcome, while those who develop the recurrence or metastasis have a poor prognosis. DOI:10.3781/j.issn.1000-7431.2014.33.536
Diagnosis and treatment of primitive neuroectodermal tumor
AbstractPrimitive neuroectodermal tumor (PNET) is a kind of malignant tumor, which most often affects children and adolescents. The incidence of PNET has risen recently. PNET has low early diagnosis rate and poor treatment effect. With the application of RT-PCR and FISH in pathological diagnosis, and MRI and PET-CT in imageological diagnosis, as well as the implementation of target treatment and multidisciplinary integrated treatment concept in the treatment, the pathogenesis, diagnosis technology and treatment means of of PNET have made remarkable progress.
Key words:
Neuroectodermal tumors, primitive; Diagnosis; Therapeutics
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.
