Trial reportThe Journal of clinical investigation2013
MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.
Trial report in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 217 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
A Phase II Study of Binimetinib in Children and Adults With NF1 Associated Plexiform Neurofibromas (PNOC010)
Developing Novel Biomarkers of Plexiform Neurofibroma Tumor Burden
Who cites it
217 citing papers in PubMed, 2 syntheses or guidelines pooled it, 330 citations in OpenAlex.
- Pooled it
- Gene signature associated with benign neurofibroma transformation to malignant peripheral nerve sheath tumors.PloS one · 2017Pooled it
- ReNeu: A Pivotal, Phase IIb Trial of Mirdametinib in Adults and Children With Symptomatic Neurofibromatosis Type 1-Associated Plexiform Neurofibroma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1.Science advances · 2024Trial
- Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial.Nature medicine · 2021Trial
- Selumetinib in Children with Inoperable Plexiform Neurofibromas.The New England journal of medicine · 2020Trial
- Target and Agent Prioritization for the Children's Oncology Group-National Cancer Institute Pediatric MATCH Trial.Journal of the National Cancer Institute · 2017Trial
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- KRAS is required for plexiform neurofibroma formation and represents a targetable vulnerability in established tumors.Science advances · 2026Article
- MAPK-dependent release of GDNF from Schwann cells mediates tumor-independent pain in neurofibromatosis 1.Science signaling · 2026Article
- Decreased PP2A expression and activity represent a therapeutic target for plexiform neurofibroma.Acta neuropathologica communications · 2026Article
- MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors.Neuro-oncology advances · 2026Review
- Neurofibromatosis type 1-plexiform neurofibromas: Integrating treatment across pediatric and adult populations.Neuro-oncology · 2026Review
- Pharmacogenomic Synthetic Lethal Screens Reveal Hidden Vulnerabilities and New Therapeutic Approaches for Treatment of NF1-Associated Tumors.Molecular cancer therapeutics · 2026Article
- Daytime SHP2 inhibitor dosing, when immune cell numbers are elevated, shrinks neurofibromas.Life science alliance · 2025Article
- Neurofibromatosis Type 1 and the Search for Effective Tumor Therapies Using High-Throughput Drug Screening.Current oncology (Toronto, Ont.) · 2025Review
- Oncological Outcome for 83 Consecutive Patients With Malignant Peripheral Nerve Sheath Tumors Treated at a Tertiary Referral Centre.Cancer reports (Hoboken, N.J.) · 2025Article
- Mirdametinib: FDA approved MEK inhibitor for neurofibromatosis type 1.Cancer chemotherapy and pharmacology · 2025Review
- Prioritization of novel agents for further investigation in pediatric non-rhabdomyosarcoma soft tissue sarcomas: A report from the Children's Oncology Group.European journal of cancer (Oxford, England : 1990) · 2025Review
- Unraveling novel variants in the NF1 gene and investigating potential therapeutic strategies.Scientific reports · 2025Article
157 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
Neurofibromatosis type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating the effects of hyperactive Ras in NF1 tumors are unknown. We performed cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs and identified global negative feedback of genes that regulate Ras/Raf/MEK/ERK signaling in both species. Nonetheless, ERK activation was sustained in mouse and human neurofibromas and MPNST. We used a highly selective pharmacological inhibitor of MEK, PD0325901, to test whether sustained Ras/Raf/MEK/ERK signaling contributes to neurofibroma growth in a neurofibromatosis mouse model (Nf1(fl/fl);Dhh-Cre) or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in more than 80% of mice tested. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide a strong rationale for testing MEK inhibitors in NF1 clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
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.