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Updated: Nov 23, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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MEK inhibitors in RASopathies

Christina Bergqvist1,2, Pierre Wolkenstein1,2,3,4

  • 1Assistance Publique-Hôpital Paris (AP-HP), Hôpital Henri-Mondor, Service de Dermatologie.

Current Opinion in Oncology
|January 4, 2021
PubMed
Abstract

Insights

MEK inhibitors (MEKi) show promise for treating RAS-driven cancers and RASopathies like Neurofibromatosis 1 (NF1). Selumetinib, a MEKi, is FDA-approved for NF1-related plexiform neurofibromas in children.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The Ras/Raf/MEK/ERK pathway regulates cell proliferation.
  • Dysregulation of this pathway is implicated in RAS-driven neoplasias and RASopathies.
  • MEK inhibitors (MEKi) have been developed as targeted therapies.

Purpose of the Study:

  • To review the role of MEK inhibitors in treating RASopathies.
  • To highlight the efficacy of MEKi in Neurofibromatosis 1 (NF1).
  • To discuss future directions for MEK inhibition in RASopathies.

Main Methods:

  • Review of early-phase clinical trials involving MEK inhibitors.
  • Analysis of data from the SPRINT trial of selumetinib in pediatric NF1 patients.
  • Evaluation of selumetinib's efficacy in low-grade gliomas (LGGs).

Main Results:

  • Selumetinib demonstrated significant tumor reduction in plexiform neurofibromas (pNF) in NF1 patients.
  • Selumetinib achieved FDA approval for pediatric symptomatic pNF.
  • Positive response rates and progression-free survival were observed in LGG patients treated with selumetinib.

Conclusions:

  • MEK inhibition is a promising and well-tolerated treatment for NF1.
  • The use of targeted agents like MEKi is expected to increase in the NF1 population.
  • Further research is needed for non-NF1 RASopathies, focusing on preclinical models and clinical trial endpoints.

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