Therapeutic Development in Neurofibromatosis

Abstract

Although neurofibromatosis (NF) was initially recognized in the nineteenth century, only in the past two decades we have witnessed a paradigm shift in therapeutics. This progress is driven by the increasing understanding of the natural history of the NF-associated tumors and understanding of the molecular landscape of these disorders. Multiple clinical trials have been launched evaluating non-surgical treatment modalities and more studies are in the pipeline. Recently, the NF community has adopted standardized endpoints recommended by the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration established in 2011. Such collaborations among academic, regulatory and supporting communities are crucial for providing the infrastructure needed for advancing the therapeutic development in the field of NF.

An Update on Neurofibromatosis Type 1-Associated Gliomas

“…Preclinical studies showing disease response to MEK inhibition have led to multiple clinical trials in NF1-related lesions [98,99]. Targeting RAS-downstream pathway signaling may provide opportunities for synergy across NF1 manifestations, as shown preclinically with MEK inhibition in plexiform neurofibromas, gliomas, and bone pathology [100][101][102]. To date, at least four MEK inhibitors have progressed to clinical trials in NF1; mirdametinib (formerly PD-0325901), trametinib (GSK1120212 Mekinist), binimetinib (ARRY-438162, MEK 162), and selumetinib (AZD6244).…”