Purpose of Review: Patients with neurofibromatosis type 1 (NF1) are at increased risk for benign and malignant neoplasms. Recently, targeted therapy with the MEK inhibitor class has helped address these needs. We highlight recent successes with selumetinib while acknowledging ongoing challenges for NF1 patients and future directions. Recent Findings: MEK inhibitors have demonstrated efficacy for NF1-related conditions, including plexiform neurofibromas and low-grade gliomas, two common causes of NF1-related morbidity. Active investigations for NF1-related neoplasms have benefited from advanced understanding of the genomic and cell signaling alterations in these conditions and development of sound preclinical animal models. Summary: Selumetinib has become the first FDA-approved targeted therapy for NF1 following its demonstrated efficacy for inoperable plexiform neurofibroma. Investigations of combination therapy and the development of a representative NF1 swine model hold promise for translating therapies for other NF1-associated pathology.
Bibliographical noteFunding Information:
Robert Galvin, Nancy Ratner, and Christopher L. Moertel declare no conflict of interest. Adrienne L. Watson is an employee and shareholder of Recombinetics, Inc., and is supported by a grant from the Children's Tumor Foundation. David A. Largaespada is the co-founder and co-owner of several biotechnology companies including NeoClone Biotechnologies, Inc., Discovery Genomics, Inc. (recently acquired by Immusoft, Inc.), B-MoGen Biotechnologies, Inc. (recently acquired by Bio-Techne Corporation), and Luminary Therapeutics, Inc. He holds equity in, serves as a Senior Scientific Advisor for and Board of Director member for Recombinetics, a genome editing company. The business of all these companies is unrelated to the contents of this article. He consults for Genentech, Inc., which funds some of his research. Sara Osum is supported by a grant from the Children's Tumor Foundation.
© 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.
- Combination therapy
- Low-grade glioma
- Malignant peripheral nerve sheath tumor
- MEK inhibitor
- Optic pathway glioma
- Plexiform neurofibroma
PubMed: MeSH publication types
- Journal Article