DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for schwannoma — screening already-approved drugs against its 48-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSchwannoma maps to a 48-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 schwannoma 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
endothelial PAS domain protein 1 (EPAS1) — EPAS1 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 furan-2-ylmethyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3H82 · 1.5 Å · ligand N-(furan-2-ylmethyl)-2-nitro-4-(trifluoromethyl)aniline (020). Experimental structure, not a prediction.
What the evidence adds up to
A 2018 in vitro and in vivo study tested Nutlin-3, an MDM2 inhibitor, and MG-132, a proteasome inhibitor, on schwannoma cells. The authors found that double genetic hits of NF2, leading to absence of the merlin protein, tended to occur in fast-growing tumours. Nutlin-3 blocked proliferation of schwannoma cells via a cooperative recovery of merlin and p53, with both proteins shuttling from cytoplasm to nucleus. Sensitivity to Nutlin-3 differed between schwannoma cells with and without merlin expression. Combining Nutlin-3 with MG-132 narrowed that difference and triggered stronger inhibitory effects on tumour growth through coordinated reactivation of p53. The study was funded by the National Natural Science Foundation of China.
A 2025 review summarises that schwannoma development is primarily linked to mutations in the NF2 gene. Merlin, the protein encoded by NF2, is integral to several signalling pathways including Ras/Raf/MEK/ERK, PI3K/Akt/mTORC1, Wnt/β-catenin, and the Hippo pathway. The review notes recent discoveries of novel genetic alterations: the SH3PXD2A::HTRA1 fusion gene, VGLL-fusions in intraparenchymal CNS schwannomas, and the SOX10 mutation particularly in non-vestibular cranial nerve schwannomas. Research is also being conducted on NF2 methylation and post-transcriptional silencing by micro RNA. The review states that advanced techniques like single-cell sequencing and multi-omics analysis have facilitated discoveries related to the tumour microenvironment and tumour heterogeneity.
Two case reports describe surgical management. A 2020 report of a primary retroperitoneal schwannoma in a 47-year-old woman states that tumour removal is the treatment of choice due to low sensitivity to radiation and chemotherapy. The patient underwent laparoscopic resection and remained stable after 4-month follow-up. A 2005 report of two intralabyrinthine schwannomas (3 mm each) in men with sudden hearing loss concludes that observation is appropriate for patients with serviceable hearing, and that in cases of vertigo a translabyrinthine or transotic approach can be used. The authors recommend regular MRI diagnostics according to a wait-and-see policy.
What remains missing are prospective clinical trials testing any drug in schwannoma patients, funding for such trials, and validated biomarkers to stratify patients by tumour growth rate or merlin expression status. The 2018 combination study has not been advanced to human testing. No drug is approved for schwannoma based on these molecular findings.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
EBioMedicine · 2018 · 21 citations · open access
Synergistic effect of Nutlin-3 combined with MG-132 on schwannoma cells through restoration of merlin and p53 tumour suppressors
AbstractBACKGROUND: The great majority of sporadic vestibular schwannomas (VSs) are due to the mutations of the NF2 gene encoding merlin. Sporadic VSs exhibit variable growth patterns and only a small fraction of the tumours are fast-growing; however, the underlying mechanisms remain undefined. METHODS: DNA sequencing and dosage analysis were used to identify the NF2 mutation status in sporadic schwannomas. The expression and sub-cellular localization of merlin and p53-MDM2 were assessed by immunoblotting, qRT-PCR and immunofluorescence. In vitro and in vivo studies were performed to reveal the effects of Nutlin-3 (a MDM2 inhibitor) and/or MG-132(a proteasome inhibitor) on schwannomas. The proliferation of schwannoma cells was assessed by CCK-8 assay, EdU staining and Flow cytometry analysis. FINDINGS: Double genetic hits of NF2 tended to occur in fast-growing tumours, characterized by the absence of merlin. The deregulation of p53-MDM2 was demonstrated to mediate merlin-deficient tumour growth, characterized by a nuclear accumulation of stabilized MDM2, contributing to a nuclear export of p53 for degradation. Nutlin-3 blocked the proliferation of schwannoma cells via a cooperative recovery of merlin and p53, accompanied by the shuttling of both proteins from the cytoplasm to the nucleus. We further demonstrated a difference in the sensitivity to Nutlin-3 between schwannoma cells with and without merlin expression. Nutlin-3 combined with MG-132 narrowed this between-group difference and triggered stronger inhibitory effects on the growth of schwannomas through coordinated reactivation of p53. INTERPRETATION: These findings present treatment strategies directed on the pathogenesis of sporadic schwannomas. FUND: National Natural Science Foundation of China.
Current molecular understanding of central nervous system schwannomas
AbstractBACKGROUND: Schwannomas are tumors that originate from myelinating Schwann cells and can occur in cranial, spinal, and peripheral nerves. Although our understanding of the molecular biology underlying schwannomas remains incomplete, numerous studies have identified various molecular findings and biomarkers associated with schwannomas of the central nervous system (CNS). The development of these tumors is primarily linked to mutations in the NF2 gene. Merlin, the protein encoded by NF2, is integral to several signaling pathways, including Ras/Raf/MEK/ERK, PI3K/Akt/mTORC1, Wnt/β-catenin, and the Hippo pathway. MAIN BODY: Recent research has also uncovered novel genetic alterations, such as the SH3PXD2A::HTRA1 fusion gene, VGLL-fusions in intraparenchymal CNS schwannomas, and the SOX10 mutation particularly in non-vestibular cranial nerve schwannomas. In addition to genetic alterations, research is also being conducted on gene expression and epigenetic regulation, with a focus on NF2 methylation and post-transcriptional silencing by micro RNA. Furthermore, the advent of advanced techniques like single-cell sequencing and multi-omics analysis has facilitated rapid discoveries related to the tumor microenvironment and tumor heterogeneity in schwannomas. CONCLUSION: A deeper exploration of these molecular findings could clarify the mechanisms of schwannoma tumorigenesis and progression, ultimately guiding the development of new therapeutic targets. This review offers a comprehensive overview of the current molecular understanding of CNS schwannomas, emphasizing the insights gained from previous research, while addressing existing controversies and outlining future research and treatment perspectives.
World Journal of Clinical Cases · 2020 · 9 citations · open access
Laparoscopic resection of primary retroperitoneal schwannoma: A case report
AbstractBACKGROUND: Schwannomas are rare, often benign, tumors deriving from Schwann cells that have low incidence in the retroperitoneal region (0.5% to 5%). Their diagnosis is hardly confirmed at early stage due to lack of specific features in signs, symptoms and imaging tests. Thus, it is necessary performing guided punch biopsy in order to identify it. Tumor removal is the treatment of choice due to its low sensitivity to radiation and chemotherapy. CASE SUMMARY: Forty-seven years old female patient who was hospitalized for elective orthopedic procedure, without complications, evolved with severe pain in the lower limbs, thigh and gluteal region associated with neurogenic claudication. Persistent pain required magnetic resonance imaging (MRI) of the lumbar spine, which showed epidural collection with dural compression and massive heterogeneous perihepatic nodular lesion. The surgical team opted for draining the collection, as well as requested an MRI of the abdomen and pelvis, whose analysis showed expansive lesion in the retroperitoneum, in close contact with the inferior vena cava and with the right renal vein. A guided puncture was performed for diagnostic clarification, which showed immunohistochemical profile compatible with schwannoma. The selected treatment comprised retroperitoneum tumor resection in association with laparoscopic cholecystectomy. The patient was discharged and remained stable after 4-mo follow-up; she remains under follow-up to check the need of cancer investigations. CONCLUSION: Schwannoma features requires surgical treatment based on laparoscopic resection, which often presents low relapse rates and optimistic prognosis.
AbstractObjective: To outline the diagnosis and management of intralabytinthine schwannomas and to propose a guideline for the treatment policy of patients. Methods/Case Reports: Diagnosing two male patients with sudden hearing loss (pure tone audiogram, caloric testing, ABR, otoacoustic emissions, HR-MRI), we found the presence of very small intralabyrinthine schwannomas. Patient 1 had normal hearing and presented a 3-mm tumor projecting to the vestibule. The cochlea was patent. Patient 2 showed severe high-frequency hearing loss without vertigo. HR-MRI revealed a 3-mm intracochlear schwannoma. Conclusions: Intralabyrinthine schwannomas are uncommon tumors that mimic the clinical features of many other neuro-otological conditions. Observation is an appropriate option for patients who have serviceable hearing. In cases of vertigo a translabyrinthine or transotic approach can be used to remove the lesion. We recommend that our patients perform regular MRI diagnostics according to a wait and see policy.
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.
