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MEK Inhibitors for Neurofibromatosis Type 1 Manifestations: Clinical Evidence and Consensus

de Blank, Peter MK; Gross, Andrea M; Akshintala, Srivandana; Blakeley, Jaishri O; Bollag, Gideon; Cannon, Ashley; Dombi, Eva; ... Fisher, Michael J; + view all (2022) MEK Inhibitors for Neurofibromatosis Type 1 Manifestations: Clinical Evidence and Consensus. Neuro-Oncology , 24 (11) pp. 1845-1856. 10.1093/neuonc/noac165. Green open access

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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 has 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 benefit 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.

Type: Article
Title: MEK Inhibitors for Neurofibromatosis Type 1 Manifestations: Clinical Evidence and Consensus
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/neuonc/noac165
Publisher version: https://doi.org/10.1093/neuonc/noac165
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Low-Grade Glioma, MEK Inhibitors, Neurofibromatosis Type 1, Plexiform Neurofibromas, RASopathy
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Developmental Biology and Cancer Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10158536
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