Therapeutic Advances in Neurofibromatosis Type 1: A Focus on Selumetinib.

Abstract

Neurofibromatosis type 1 (NF1) is a genetic condition inherited in an autosomal dominant pattern, but with 50% of cases caused by de novo mutations. Neurofibromin, the gene product in NF1, regulates the RAS/MAPK pathway, and mutation can lead to cell proliferation and the development of tumours. NF1 often presents in childhood with cafe-au-lait macules, skinfold freckling, nervous system tumours, and phenotypically variable findings. Plexiform neurofibromas (PN), a type of peripheral nerve sheath tumour seen in NF1, are typically histologically benign. However, PN can cause significant physical disfigurement, pain, and decreased quality of life, and have historically been difficult to treat. Selumetinib, a MEK inhibitor inhibiting the RAS/MAPK pathway, was Health Canada approved in 2022 for the treatment of symptomatic, inoperable PN in individuals with NF1 aged 2 years and older. Phase 1 and 2 trials have demonstrated reduced tumour size, decreased disfigurement and pain, and increased quality of life.