MEK inhibitors for neurofibromatosis type 1 manifestations: Clinical evidence and consensus.
MEK inhibitors
RASopathy
low-grade glioma
neurofibromatosis type 1
plexiform neurofibromas
Journal
Neuro-oncology
ISSN: 1523-5866
Titre abrégé: Neuro Oncol
Pays: England
ID NLM: 100887420
Informations de publication
Date de publication:
02 11 2022
02 11 2022
Historique:
pubmed:
6
7
2022
medline:
4
11
2022
entrez:
5
7
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35788692
pii: 6631282
doi: 10.1093/neuonc/noac165
pmc: PMC9629420
doi:
Substances chimiques
Mitogen-Activated Protein Kinase Kinases
EC 2.7.12.2
Protein Kinase Inhibitors
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1845-1856Subventions
Organisme : NCATS NIH HHS
ID : KL2 TR001854
Pays : United States
Organisme : NICHD NIH HHS
ID : P50 HD105351
Pays : United States
Organisme : NHLBI NIH HHS
ID : R35 HL135742
Pays : United States
Organisme : NCI NIH HHS
ID : U54 CA196519
Pays : United States
Informations de copyright
Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2022.
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