MEK Inhibitors for Neurofibromatosis Type 1-Associated Central and Peripheral Nervous System Tumors

Abstract Neurofibromatosis type 1 (NF1)-associated tumors typically develop in the setting of bi-allelic inactivation of the NF1 gene and resultant overactivation of the Ras/mitogen-activated protein kinase signaling pathway. Mitogen-activated protein kinase kinase (MEK) inhibitors target the downstream effectors of Ras and have shown promising activity for NF1-associated tumors. Several recent and ongoing clinical trials have demonstrated both the safety and efficacy of MEK inhibitors for plexiform neurofibroma (PN) and low-grade glioma, with the phase 1/2 study of selumetinib supporting the first regulatory approval of a medical therapy for PN. The relative successes of MEK inhibitors for the treatment of PN has created an exciting and hopeful era for patients, families, and clinicians alike providing the momentum and significant interest in expanding the use of MEK inhibitors across tumor types in NF1. Herein, we review the landscape of past and present clinical trials and supporting evidence for the use of MEK inhibitors in NF1-associated tumors.