Deficiency of the tumor suppressor protein merlin leads to the development of benign tumors of the nervous system such as schwannomas, ependymomas and meningiomas. These tumors can occur spontaneously or as part of a tumor predisposition syndrome called neurofibromatosis type 2 (NF2), which involves multiple tumors. Schwannomas are the hallmark tumors of NF2 and are the most frequent and well-characterized of the merlin-deficient tumors. Surgery or radiotherapy are used to treat single tumors and can leave the patient with substantial morbidity. Limitations of other treatment options for merlin-deficient tumors, such as the lack of effectiveness of chemotherapy, have led to an urgent requirement for new pharmaceutical therapies. Merlin-deficient tumors are genetically well-defined, which allows rational testing of new molecular therapies that have been developed and successfully used to treat various cancers in the past few years. This Review centers on four key families of receptor tyrosine kinases—the ErbB family, platelet-derived growth factor receptor β, insulin-like growth factor 1 receptor, and vascular endothelial growth factor receptors—focusing on their role in schwannoma pathobiology and the therapeutic potential of targeting these receptors and their downstream signaling pathways.
Deficiency of the tumor suppressor protein merlin leads to a high burden of benign tumors—most commonly schwannomas, but also meningiomas and ependymomas
Emerging preclinical and clinical data suggest that prevention of tumor growth and survival by inhibiting the receptor tyrosine kinases ErbB2, platelet-derived growth factor receptor β, and insulin-like growth factor 1 receptor could be a promising therapeutic strategy
Drugs targeting vascular endothelial growth factor receptor signaling, which inhibit tumor vascularization, are also currently in phase II trials for schwannoma
Inhibiting multiple targets or a single downstream target that is common to several pathways may be the most effective approach and could help to limit adverse effects associated with long treatment times
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Ammoun, S., Hanemann, C. Emerging therapeutic targets in schwannomas and other merlin-deficient tumors. Nat Rev Neurol 7, 392–399 (2011). https://doi.org/10.1038/nrneurol.2011.82
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