Pathogenesis and management of type 2 neurofibromatosis

Abstract

Introduction: The molecular pathogenesis of the inherited tumour predisposition syndrome, neurofibromatosis type 2 (NF2), has been the subject of intense scrutiny in recent years. Better understanding of the multiple physiological roles of the NF2 protein Merlin, and increasing availability of molecularly targeted therapies have for the first time made medical treatments a feasible option for patients with NF2.

Areas covered: In this report we describe the clinical features of NF2, we summarise recent advances in NF2 biology and describe the evidence underlying current management, focusing particularly on the activity of anti-angiogenic agents and on therapies that target Merlin’s interaction partners.

Expert opinion: The anti-angiogenic agent bevacizumab is the first medical therapy to show real promise in the treatment of this disease, but its effects are limited to disease stabilisation and to partial imaging and hearing responses. The results of early-phase trials targeted towards Merlin’s partners have been disappointing to date, but given the breadth of Merlin’s interactions, it may be unrealistic to expect single pathway inhibition to have a measurable effect. Future work should focus on rational combinations of targeted agents and on studies to ameliorate the phenotypic features of NF2, rather than focusing solely on the management of established tumours.

Keywords:

• bevacizumab
• gamma knife
• neurofibromatosis type 2
• schwannoma
• targeted therapy

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Notes

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