Targeted Therapies for the Neurofibromatoses

Simple Summary The neurofibromatoses-neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis-are genetic tumor predisposition syndromes in which affected patients are at risk for the development of nerve-associated central and peripheral tumors. Patients often develop multiple tumors which can result in significant symptoms and morbidity. Treatment of the tumors associated with these disorders has evolved over the past decade, including significant work focused on inhibition of the signaling dysregulation and symptom minimization. This review outlines the most common tumor types associated with each of these syndromes and the current progress in therapeutic options. Over the past several years, management of the tumors associated with the neurofibromatoses has been recognized to often require approaches that are distinct from their spontaneous counterparts. Focus has shifted to therapy aimed at minimizing symptoms given the risks of persistent, multiple tumors and new tumor growth. In this review, we will highlight the translation of preclinical data to therapeutic trials for patients with neurofibromatosis, particularly neurofibromatosis type 1 and neurofibromatosis type 2. Successful inhibition of MEK for patients with neurofibromatosis type 1 and progressive optic pathway gliomas or plexiform neurofibromas has been a significant advancement in patient care. Similar success for the malignant NF1 tumors, such as high-grade gliomas and malignant peripheral nerve sheath tumors, has not yet been achieved; nor has significant progress been made for patients with either neurofibromatosis type 2 or schwannomatosis, although efforts are ongoing.