DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for plexiform neurofibroma — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePlexiform neurofibroma maps to a 6-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
approvedTrametinibApproved drug
Structures already discussed alongside plexiform neurofibroma 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 KSR2:MEK1 — Trametinib has a real, experimentally solved structure in complex with this target (PDB 7JUR, 2.82 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 qomdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7JUR · 2.82 Å · ligand Trametinib (QOM). Experimental structure, not a prediction.
What the evidence adds up to
A 2008 case report described one child with plexiform neurofibroma and severe pain who was given alpha-interferon; the abstract provides no outcome data, no tumour shrinkage, and no pain response. A 1959 surgical series of 11 children reported that resectable lesions could be removed locally, sometimes requiring repeated operations over years, and that patients could then have no further trouble for a long time. A 2009 review states that diagnosis is primarily clinical and that MRI may aid management; it offers no treatment results.
A 2021 case study of a 9-month-old infant with a life-threatening plexiform neurofibroma identified germline mutations in NF1 and LZTR1, plus a somatic GNAZ variant that increased ERK 1/2 activation in cell assays. After treatment with the MEK inhibitor trametinib, the authors observed prominent clinical improvement in that single patient. The same paper notes that plexiform neurofibroma phenotype varies from indolent to locally aggressive and suggests that non-NF1 modifier genes contribute to severity.
A 2025 study of 9 cases of dendritic cell neurofibroma with pseudorosettes found recurrent PRKCA gene fusions (SLC44A1::PRKCA) and argues that this tumour is molecularly distinct from conventional neurofibroma and from plexiform neurofibroma. The authors warn that its multinodular architecture can be confused with plexiform neurofibroma, leading to unnecessary clinical work-up for neurofibromatosis type 1.
What is still missing: no randomised trial of any drug for plexiform neurofibroma is reported in these abstracts; the interferon and MEK inhibitor evidence rests on single cases. No prospective data define which patients with aggressive disease carry modifier genes, and no validated biomarker stratifies indolent from life-threatening tumours. Surgical series lack standardised outcome measures and long-term follow-up beyond local recurrence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pediatric Hematology and Oncology · 2008 · 16 citations
MANAGEMENT OF PLEXIFORM NEUROFIBROMA WITH INTERFERON ALPHA
AbstractElvan Caglar Citak MDa*, Aynur Oguz MDa, Ceyda Karadeniz MDa, Arzu Okur MDa, Leyla Memis MDb & Oznur Boyunaga MDca Gazi University Faculty of Medicine, Department of Pediatric Oncology, Ankara, Turkeyb Gazi University Faculty of Medicine, Department of Pathology, Ankara, Turkeyc Gazi University Faculty of Medicine, Department of Pediatric Radiology, Ankara, Turkey† Correspondence: Elvan Caglar Citak, MD, Huseyin Onat Sokak 15/13, Asagiayranci/Ankara, TurkeyPlexiform neurofibroma is a relatively common but potentially devastating manifestation of neurofibromatosis type 1 (NF 1). A substantial number of plexiform neurofibroma causes morbidity. Various treatment modalities are considered to decrease pain. In this paper a case with plexiform neurofibroma causing severe pain and in whom alpha-interferon was used is presented.
International Journal of Dermatology · 2009 · 13 citations
Plexiform neurofibromas in neurofibromatosis type 1
AbstractPlexiform neurofibroma developing in neurofibromatosis type 1 is a fascinating overture whereby diagnosis is primarily based on clinical characteristics, the details of which are outlined. Nonetheless, it is imperative to establish a clear-cut clinical status vis-á-vis the adjoining tissues. Magnetic resonance imaging (MRI) may provide an additional supplement to the diagnosis and an aid to further management of the condition.
EXPERIENCES WITH THE MANAGEMENT OF PLEXIFORM NEUROFIBROMA
AbstractPlexiform neurofibroma is a relatively uncommon manifestation of diffuse neurofibromatosis and is characterized by its unique gross appearance. Because of its tendency to involve peripheral nerves centripetally it must be vigorously treated surgically to prevent damage to vital areas, notably the brain and spinal cord, although the tumor is basically benign. We have presented our experience with 11 children who had this disease, demonstrating that despite the propensity for the growth to crop up in several areas it can be eradicated locally, and the patient may have no further trouble for a long time. We believe that resectable lesions should be removed even though this may require repeated operations over a period of several years.
Concomitant variants in <i>NF1</i>, <i>LZTR1</i> and <i>GNAZ</i> genes probably contribute to the aggressiveness of plexiform neurofibroma and warrant treatment with MEK inhibitor
AbstractNeurofibromatosis 1 (NF1) is caused by germline mutations in the NF1 gene and manifests as proliferation of various tissues, including plexiform neurofibromas. The plexiform neurofibroma phenotype varies from indolent to locally aggressive, suggesting contributions of other modifiers in addition to somatic loss of NF1. In this study, we investigated a life-threatening plexiform neurofibroma in a 9-month-old female infant with NF1. Germline mutations in two RASopathy-associated genes were identified using whole-exome sequencing-a de novo pathogenic variant in the NF1 gene, and a known pathogenic variant in the LZTR1 gene. Somatic analysis of the plexiform neurofibroma revealed NF1 loss of heterozygosity and a variant in GNAZ, a gene encoding a G protein-coupled receptor. Cells expressing mutant GNAZ exhibited increased ERK 1/2 activation compared to those expressing wild-type GNAZ. Taken together, we suggest the variants in NF1, LZRT1 and GNAZ act synergistically in our patient, leading to MAPK pathway activation and contributing to the severity of the patient's plexiform neurofibromatosis. After treatment with the MEK inhibitor, trametinib, a prominent clinical improvement was observed in this patient. This case study contributes to the knowledge of germline and somatic non-NF1 variants affecting the NF1 clinical phenotype and supports use of personalized, targeted therapy.
The American Journal of Surgical Pathology · 2025 · 1 citations
Protein Kinase C-alpha Gene Fusions in Dendritic Cell Neurofibroma
AbstractDendritic cell neurofibroma with pseudorosettes is an uncommon but distinctive variant of neurofibroma. The pseudorosette structures are formed by the circumferential arrangement of small, dark cells around an eosinophilic core at the center of which there is often a single larger and paler cell with slender dendrite-like projections. Dendritic cell neurofibroma often shows a multinodular architecture, which can cause confusion with plexiform neurofibroma. Since plexiform neurofibroma is essentially pathognomonic of Neurofibromatosis type I, such confusion could lead to unnecessary and costly clinical work-up. Since its description in 2001, there has been controversy as to whether dendritic cell neurofibroma represents a true subtype of neurofibroma, whose defining molecular feature is loss-of-function mutation in NF1 . Here we show in a series of 9 cases that dendritic cell neurofibroma harbors recurrent gene fusions involving protein kinase c-alpha ( PRKCA ), including SLC44A1::PRKCA . Identical gene fusions are known to occur in a rare brain tumor known as papillary glioneuronal tumor, although this entity appears to be morphologically and clinically distinct from dendritic cell neurofibroma. Our results distinguish dendritic cell neurofibroma from conventional types of neurofibroma and raise consideration that dendritic cell neurofibroma may be better classified as a unique type of benign neural tumor.
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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