DeCure for Spinal Cord Primitive Neuroectodermal Tumor
DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for Spinal Cord Primitive Neuroectodermal Tumor — 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 moduleSpinal Cord Primitive Neuroectodermal Tumor 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
approvedMelatoninMelatonin receptor agonist
Structures already discussed alongside spinal cord primitive neuroectodermal tumor 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 fad quinone reductase 2 — Melatonin has a real, experimentally solved structure in complex with this target (PDB 4QOG, 1.4 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 ml1drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4QOG · 1.4 Å · ligand Melatonin (ML1). Experimental structure, not a prediction.
What the evidence adds up to
The DCC gene, a proposed tumour suppressor, encodes a transmembrane receptor for netrins, which are axon guidance factors in the developing spinal cord. When netrin is absent or at low levels, DCC can promote apoptosis. One DCC allele is deleted in roughly 70% of colorectal cancers, and DCC expression is often reduced or absent in those tissues. However, the rarity of point mutations in DCC coding sequences, the lack of a tumour predisposition in mice heterozygous for DCC inactivation, and the presence of other candidate tumour suppressor genes on chromosome 18q have raised questions about DCC’s role in cancer.
Spinal primitive neuroectodermal tumours (PNETs) are aggressive malignancies. Patients typically have short survival times despite maximal surgery, chemotherapy, and radiation. No standard management guidelines exist. In one reported case, a 36-year-old woman with a cervical intraspinal PNET underwent surgical resection and radiotherapy. MRI identified local recurrence in the spinal canal three months after surgery. The authors concluded that optimal therapy has not yet been found, and that multidisciplinary treatment requires further clinical investigation.
No study in these abstracts tests any drug for spinal PNET. The DCC review concerns colorectal cancer, not spinal PNET, and does not report any therapeutic intervention. The spinal PNET case reports describe surgery and radiotherapy, not drug treatment.
What is missing: any clinical trial of a drug for spinal PNET, any evidence linking DCC or netrin signalling to treatment of this tumour type, and any patient stratification or funding for such studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Oncology · 2004 · 130 citations
Role of the Dependence Receptor DCC in Colorectal Cancer Pathogenesis
AbstractMore than a decade ago, the DCC (deleted in colorectal cancer) gene was proposed as a putative tumor suppressor gene. Data supporting this proposal included observations that one DCC allele was deleted in roughly 70% of colorectal cancers, some cancers had somatic mutations of the DCC gene, and DCC expression was often reduced or absent in colorectal cancer tissues and cell lines. Despite subsequent studies which have supported DCC's potential role as a tumor suppressor gene, the rarity of point mutations identified in DCC coding sequences, the lack of a tumor predisposition phenotype in mice heterozygous for DCC inactivating mutations, and the presence of other known and candidate tumor suppressor genes on chromosome 18q have raised questions about DCC's candidacy. Following its initial characterization, the DCC protein was identified as a transmembrane receptor for netrins, key factors in axon guidance in the developing nervous system. At first glance, the established role of DCC and netrin-1 during organization of the spinal cord could be viewed as a further challenge to the position that DCC inactivation might play a significant role in tumorigenesis. However, recent observations on DCC's functions in intracellular signaling have renewed interest in the potential contribution of DCC inactivation to cancer. In particular, data indicate that, when engaged by netrin ligands, DCC may activate downstream signaling pathways. Moreover, in settings where netrin is absent or at low levels, DCC can promote apoptosis. Here, we review DCC's candidacy as a tumor suppressor gene, with an emphasis on how recent molecular analyses of DCC have offered support for the notion that DCC may function as a tumor suppressor gene.
Neurosurgical FOCUS · 2010 · 53 citations · open access
Primitive neuroectodermal tumors of the spine: a comprehensive review with illustrative clinical cases
AbstractPrimary spinal primitive neuroectodermal tumors (PNETs) are uncommon malignancies that are increasingly reported in the literature. Spinal PNETs, like their cranial counterparts, are aggressive tumors and patients with these tumors typically have short survival times despite maximal surgery, chemotherapy, and radiation. Because no standard management guidelines exist for treating these tumors, a multitude of therapeutic strategies have been employed with varying success. In this study the authors perform a comprehensive review of the literature on primary spinal PNETs and provide 2 new cases that highlight the salient features of their clinical management.
Reports of Practical Oncology & Radiotherapy · 2015 · 30 citations · open access
Oral administration of melatonin modulates the expression of tumor necrosis factor-α (TNF-α) gene in irradiated rat cervical spinal cord
AbstractAIM: We aimed to determine the changes in TNF-α expression and Malondialdehyde (MDA) level in a short time after irradiation. Furthermore, we evaluated the effect of melatonin on the modulation of TNF-α gene expression. BACKGROUND: The radio-sensitivity of the cervical spinal cord limits the dose of radiation which can be delivered to tumors in the neck region. There is increasing evidence that TNF-α has a role in the development of the acute phase of spinal cord injury. MATERIALS/METHODS: Four groups of rats were investigated. Group 1 (vehicle treatment) served as the control. Group 2 (radiation) was treated with the vehicle, and 30 min later, the rats were exposed to radiation. Group 3 (radiation + melatonin) was given an oral administration of melatonin (100 mg/kg body weight) and 30 min later exposed to radiation in the same manner as in group 2. Group 4 (melatonin-only) was also given an oral administration of melatonin (100 mg/kg body weight). 5 mg/kg of melatonin was administered daily to rats in groups 3 and 4, and the vehicle was administered daily to rats in groups 1 and 2. RESULTS: Three weeks after irradiation, TNF-α gene up-regulated almost 5 fold in the irradiated group compared to the normal group. TNF-α gene expression in the melatonin pretreatment group, compared to the radiation group, was significantly down-regulated 3 weeks after irradiation (p < 0.05). MDA levels increased after irradiation and then significantly decreased under melatonin treatment. CONCLUSION: We suggest that inhibition of TNF-α expression by oral administration of melatonin may be a therapeutic option for preventing radiation-induced spinal cord injury.
Case report of cervical intraspinal primitive neuroectodermal tumor and literature review
AbstractObjective To investigate the clinical characters and therapy of primitive neuroectodermal tumor(PNET).Methods A retrospective analysis was conducted.A 36-year-old female patient was showed pain and numbness of the right upper limb and back for 6 months.The cervical spine MRI showed a spindleshaped intradural mass right ventrolateral of spinal cord at C5-7 with in homogeneously enhancing.Surgery and pathologic examination confirmed that was PNET.Combiled with a series of literatures to analyse the clinical characters Results Surgery was performed to remove the tumor and decompression combined with radiotherapy.The pathologic examination and immunohistochemical analysis revealed that it was PNET.MRI identified local recurrence in spinal canal at 3 month later after surgery.Conclusion Spinal PNET is an uncommon intraspinal tumor with poor prognosis.Histopathology is the evidence of diagnosis.Optimal therapy has not yet been found.Surgical resection with the combination of chemo-radiotherapy or radiotherapy might get the better outcomes.Multidisciplinary treatment should be further clinical required.
Key words:
Primitive neuroectodermal tumor; Cervical spine; Spine canal
Clinical Cancer Investigation Journal · 2016 · 0 citations · open access
Primary primitive neuroectodermal tumor of spinal cord
AbstractPrimarily spinal primitive neuroectodermal tumors are rare neoplasm. A 28-year-old female presented with complaints of pain in lower back, radiating to both lower limbs. Magnetic resonance imaging scan of the lumbosacral spine showed an intradural extramedullary space-occupying lesion. The patient underwent L2–L5 laminectomy with excision of the lesion. Histopathology and immunohistochemistry reports confirmed the diagnosis of primitive neuroectodermal tumor while a thorough metastatic workup ru
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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