New developments in neurofibromatosis type 2 and vestibular schwannoma

Yin Ren, Divya A Chari, Sasa Vasilijic, D Bradley Welling, Konstantina M Stankovic, Yin Ren, Divya A Chari, Sasa Vasilijic, D Bradley Welling, Konstantina M Stankovic

Abstract

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized by the development of multiple nervous system tumors due to mutation in the NF2 tumor suppressor gene. The hallmark feature of the NF2 syndrome is the development of bilateral vestibular schwannomas (VS). Although there is nearly 100% penetrance by 60 years of age, some patients suffer from a severe form of the disease and develop multiple tumors at an early age, while others are asymptomatic until later in life. Management options for VS include surgery, stereotactic radiation, and observation with serial imaging; however, currently, there are no FDA-approved pharmacotherapies for NF2 or VS. Recent advancements in the molecular biology underlying NF2 have led to a better understanding of the etiology and pathogenesis of VS. These novel signaling pathways may be used to identify targeted therapies for these tumors. This review discusses the clinical features and treatment options for sporadic- and NF2-associated VS, the diagnostic and screening criteria, completed and ongoing clinical trials, quality of life metrics, and opportunities for future research.

Keywords: NF2; acoustic neuroma; clinical trials; drug repositioning; hearing loss; neurofibromatosis type 2; vestibular schwannoma.

© The Author(s) 2020. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.

Figures

Figure 1.
Figure 1.
Schematic illustrating vestibular schwannoma arising from a vestibular nerve within the internal auditory canal. The figure was modified from SMART (Servier Medical Art), licensed under a Creative Common Attribution 3.0 Generic License. http://smart.servier.com/.
Figure 2.
Figure 2.
Merlin-regulated signaling pathways and current therapeutic targets in vestibular schwannoma. Merlin protein suppresses cell growth and proliferation by acting at multiple levels in a cell. Details are included in Supplementary Materials.
Figure 3.
Figure 3.
Examples illustrating that vestibular schwannoma (VS) size does not correlate with hearing loss. PTA, pure tone average. Yellow arrow points to VS in all scans. Details are included in Supplementary Materials.

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