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An Orthotopic Sciatic Nerve Xenograft for Neurofibromatosis Type 1 Neurofibromas
Published on: October 10, 2025
MEK inhibitors for neurofibromatosis type 1-associated central and peripheral nervous system tumors
Chelsea Kotch1, Peter de Blank2, Jason Fangusaro3
1Children's Hospital of Philadelphia, Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania (C.K., M.J.F.).
Abstract:
Neurofibromatosis type 1 (NF1)-associated tumors typically develop in the setting of biallelic inactivation of the NF1 gene and resultant overactivation of the Ras/mitogen-activated protein kinase signaling pathway. Mitogen-activated protein kinase kinase (MEK) inhibitors target the downstream effectors of Ras and have shown promising activity for NF1-associated tumors. Several recent and ongoing clinical trials have demonstrated both the safety and efficacy of MEK inhibitors for plexiform neurofibroma (PN) and low-grade glioma, with the phase 1/2 study of selumetinib supporting the first regulatory approval of a medical therapy for PN. The relative successes of MEK inhibitors for the treatment of PN have created an exciting and hopeful era for patients, families, and clinicians alike providing the momentum and significant interest in expanding the use of MEK inhibitors across tumor types in NF1. Herein, we review the landscape of past and present clinical trials and supporting evidence for the use of MEK inhibitors in NF1-associated tumors.
Insights
Mitogen-activated protein kinase kinase (MEK) inhibitors show promise for treating Neurofibromatosis type 1 (NF1)-associated tumors. Clinical trials demonstrate their safety and efficacy, particularly for plexiform neurofibroma, heralding a new treatment era.
Area of Science:
- Oncology
- Genetics
- Pharmacology
Background:
- Neurofibromatosis type 1 (NF1) involves biallelic NF1 gene inactivation, leading to Ras/mitogen-activated protein kinase pathway overactivation.
- This pathway dysregulation drives the development of NF1-associated tumors.
Purpose of the Study:
- To review the clinical trial landscape and evidence for MEK inhibitors in NF1-associated tumors.
- To highlight the expanding therapeutic potential of MEK inhibitors across various NF1 tumor types.
Main Methods:
- Review of past and present clinical trials involving MEK inhibitors for NF1 tumors.
- Analysis of supporting evidence for MEK inhibitor efficacy and safety.
Main Results:
- MEK inhibitors demonstrate promising activity and have shown safety and efficacy in clinical trials for NF1-associated tumors.
- Selumetinib's success in treating plexiform neurofibroma led to its first regulatory approval for this indication.
- Significant interest exists in expanding MEK inhibitor use to other NF1 tumor types.
Conclusions:
- MEK inhibitors represent a significant advancement in the treatment of NF1-associated tumors.
- The success in plexiform neurofibroma supports further investigation and application of MEK inhibitors in other NF1-related malignancies.
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