Current status of MEK inhibitors in the treatment of plexiform neurofibromas
Abstract
Background Neurofibromatosis type 1 (NF1)-related plexiform neurofibromas (pNF) can be debilitating and until recently, surgery was the only potentially effective therapy for these tumors.Methods We review critical steps in the path towards the FDA approval of the first medical therapy for NF1 pNF and the current status of MEK inhbitor therapy.Results Sustained efforts by the NF community have resulted in a detailed understanding of the natural history and biology of NF1-related peripheral nerve sheath tumors. This work provided the basis for the development of meaningful clinical trials targeting pNF. Inhibition of the RAS/MAPK signaling pathway with MEK inhibitors identified the first medical therapy which resulted in shrinkage in the majority of children with NF1 and large inoperable pNF. Based on this finding and subsequent demonstration of clinical benefit, the MEK inhibitor selumetinib recently received approval by the United States Food and Drug Administration (FDA) for children with symptomatic pNF.Conclusions Sustained efforts and collaborations have resulted in identification of MEK inhibitors as effective therapy for NF1 pNF. Future work work will be directed at prevention of pNF morbidity and deepening the reponse in symptomatic pNF.
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Pan-KRAS inhibitors and degraders could be prime choice for cancers driven by wild-type KRAS, such as KRAS wild-type amplified or NF1 loss, and Neurofibromatosis type 1.
“Pan-KRAS inhibitors and degraders could also become the prime choice for cancers driven by wild-type KRAS, such as KRAS wild-type amplified or cancers driven by loss of the NF1 tumor suppressor, as well as Neurofibromatosis type 1 or its associated malignancies (34, 62, 63).”
From Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants (2022) · cites this paper as [63]
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Expanding the Reach of Precision Oncology by Drugging All <i>KRAS</i> Mutants
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- Authors
- Gross, A. M., Dombi, E., & Widemann, B. C.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Widemann, Brigitte C.
- Venue
- Child's Nervous System
- Published
- 2020-06-30
- Volume
- 36
- Issue
- 10
- Pages
- 2443-2452
- ISSN
- 0256-7040 (ISSN-L)
- 1433-0350
- OpenAlex
- W3040570144
- Cited by
- 47
- References
- 59
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 15 · 2020: 3
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Child s Nervous System (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Neurology › Neurofibromatosis and Schwannoma Cases
- Health Sciences › Medicine › Neurology › Neuroblastoma Research and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- plexiform neurofibroma, neurofibromatosis type 1, MEK inhibitors, selumetinib, RAS/MAPK pathway, peripheral nerve sheath tumor, FDA approval, childhood cancer treatment, unresectable tumors
- MeSH terms
- Child, Humans, Neurofibromatosis 1, Nerve Sheath Neoplasms, Neurofibroma, Plexiform, Mitogen-Activated Protein Kinase Kinases, Protein Kinase Inhibitors
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