Author(s)

Jingzi Guo, Jingwen Li, Xuanxuan Li, Chunnan Zhou

Corresponding Author

Jingwen Li

ABSTRACT

Neurofibromatosis type 1 (NF1) is a prevalent genetic neurocutaneous disease globally and may result in various complications. Among these complications, cancer is the leading cause of death. Patients with NF1 have a high possibility of plexiform neurofibroma (PN), which may later transform into malignant peripheral nerve sheath. Treatment of NF1 is case-to-case based considering the variety of complications. For NF1 patients with PN, surgery is the standard solution. However, due to the complexity of nerves and the difficulty of performing surgeries, resorting to surgery is not merely effective. The preclinical trials on mice with plexiform neurofibroma indicated that selumetinib (commercial name, Koselugo) has a positive effect in NF1 disease in case of shrinkage in the size of the tumor. Similar results were obtained when conducting the first-in-human trials. Safety and side effects of selumetinib were also evaluated by a phase I trial of the drug in pediatric patients with recurrent or refractory low-grade glioma. In addition, Selumetinib is an inhibitor of mitogen-activated protein kinase 1 or 2 (MEK) essential for the MAPK signaling pathway of tumorigenesis. The inhibition caused by selumetinib precludes the activation of MEK1/2 and transcription factors, which stops the cellular proliferation of cancer cells. This comprehensive review introduces Selumetinib and its mechanism of inhibiting the proliferation of Neurofibromatosis cells, focusing on the completed and ongoing clinical trials to provide a reference for clinicians to make better clinical decisions.

KEYWORDS

Selumetinib, neurofibromatosis type 1 (NF1), plexiform neurofibroma (PN), Mitogen-activated protein kinase (MAPK-ERK1/2)