ArticleNeuro-oncology advances
Selumetinib normalizes Ras/MAPK signaling in clinically relevant neurofibromatosis type 1 minipig tissues in vivo.
Article in Neuro-oncology advances. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 8 citations in OpenAlex.
- Integrative Multi-Omics and Single-Cell Profiling Identify Chitinase Domain Containing Protein 1 (CHID1) as a Prognostic Biomarker in Glioblastoma.Journal of Cancer · 2026Article
- Combining nonsense mutation suppression therapy with nonsense-mediated decay inhibition in neurofibromatosis type 1.Molecular therapy. Nucleic acids · 2023Article
- Existing and Developing Preclinical Models for Neurofibromatosis Type 1-Related Cutaneous Neurofibromas.The Journal of investigative dermatology · 2023Review
- Evaluation of NF1 and RASA1 gene expression in endometriosis.European journal of obstetrics & gynecology and reproductive biology: X · 2022Article
- Review
- Spontaneous and Engineered Large Animal Models of Neurofibromatosis Type 1.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe MEK1/2 inhibitor selumetinib was recently approved for neurofibromatosis type 1 (NF1)-associated plexiform neurofibromas, but outcomes could be improved and its pharmacodynamic evaluation in other relevant tissues is limited. The aim of this study was to assess selumetinib tissue pharmacokinetics (PK) and pharmacodynamics (PD) using a minipig model of NF1.
methodsWT (
resultsKey selumetinib PK parameters aligned with those observed in human patients. Selumetinib concentrations were higher in CNS tissues from NF1 compared to WT animals. Inhibition of ERK phosphorylation was achieved in PBMCs (mean 60% reduction), skin (95%), and sciatic nerve (64%) from all minipigs, whereas inhibition of ERK phosphorylation in cerebral cortex was detected only in NF1 animals (71%). Basal p-ERK levels were significantly higher in NF1 minipig optic nerve compared to WT and were reduced to WT levels (60%) with selumetinib. Modulation of transcript biomarkers was observed in all tissues.
conclusionsSelumetinib reduces MAPK signaling in tissues clinically relevant to NF1, effectively normalizing p-ERK to WT levels in optic nerve but resulting in abnormally low levels of p-ERK in the skin. These results suggest that selumetinib exerts activity in NF1-associated CNS tumors by normalizing Ras/MAPK signaling and may explain common MEK inhibitor-associated dermatologic toxicities.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.