Neurofibromatosis type 2 (NF2) is an inherited tumor predisposition syndrome leading to the formation of vestibular schwannomas (VS) and other central nervous system (CNS) tumors. Clinical NF2 follows a genetic alteration to the NF2 gene, which disrupts the function of a cell membrane-related protein, merlin. Though the role of merlin is incompletely understood, it is predominantly thought to achieve tumor suppressive effects by affecting multiple signaling pathways important for contact inhibition, cellular proliferation, and cellular growth. Patients with NF2 have a bimodal age of onset in children and young adults, with the former tending to present with a more severe phenotype involving multiple tumors. Currently available treatments are non-curative. Surgical resection is the mainstay for growing tumors but comes at the cost of significant morbidity, while radiotherapy is generally not advisable due to the risk of secondary malignancy and malignant transformation. Hence, there remains a critical demand for effective anti-neoplastic therapies for NF2-related tumors. There are currently no FDA-approved biologic therapies for the treatment of NF2. Given the complexity and far-reaching effects of Merlin, multiple molecular targets and pathways have been investigated and are currently at various stages of investigation.
Part of the book: Neurofibromatosis