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MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus

Authors :
Peter M K de Blank
Andrea M Gross
Srivandana Akshintala
Jaishri O Blakeley
Gideon Bollag
Ashley Cannon
Eva Dombi
Jason Fangusaro
Bruce D Gelb
Darren Hargrave
AeRang Kim
Laura J Klesse
Mignon Loh
Staci Martin
Christopher Moertel
Roger Packer
Jonathan M Payne
Katherine A Rauen
Jonathan J Rios
Nathan Robison
Elizabeth K Schorry
Kevin Shannon
David A Stevenson
Elliot Stieglitz
Nicole J Ullrich
Karin S Walsh
Brian D Weiss
Pamela L Wolters
Kaleb Yohay
Marielle E Yohe
Brigitte C Widemann
Michael J Fisher
Source :
Neuro Oncol, Neuro-Oncology, vol 24, iss 11
Publication Year :
2023

Abstract

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefits for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low-grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts.

Details

ISSN :
15235866
Volume :
24
Issue :
11
Database :
OpenAIRE
Journal :
Neuro-oncology
Accession number :
edsair.doi.dedup.....fdc09be891aa248dab39ba370d386094