Mirdametinib approval for neurofibromatosis type 1 with inoperable plexiform neurofibromas: the journey of MEK inhibitors

Neurofibromatosis type I (NF-1) is an autosomal dominant genetic disorder, regularly accompanied by plexiform neurofibroma.Surgical intervention for plexiform neurofibromas is reserved for high-risk cases, while recent studies have explored various treatments, including mitogen-activated protein kinase kinase (MEK) inhibitors, which target the RAS/mitogen-activated protein kinase (MAPK) pathway, a key driver of NF1-associated tumorigenesis.The United States Food and Drug Administration (FDA) has recently approved mirdametinib for adult and pediatric NF-1 patients aged 2 years or older with symptomatic and inoperable plexiform neurofibroma in view of its significant impact on tumor volume reduction.In this article, we review the current evidence on mirdametinib's mechanisms of action and effectiveness in the management of NF-1.