Molecular biology and disease models of vestibular schwannomas: State of the art.

Vestibular schwannomas arise either sporadically or as part of the familial condition NF2-related schwannomatosis. Almost all schwannomas arise due to the loss of the NF2 tumor suppressor gene, encoding the Merlin protein, and cause a slow-growing tumor composed largely of not only undifferentiated Schwann cells but also immune cells and newly formed blood vessels. They most commonly arise on the eighth cranial nerve, the vestibulocochlear nerve, but may occur on other cranial or peripheral nerves. With surgery and/or radiotherapy currently being the only treatment options, there have been many attempts to develop a robust disease model for this important tumor type to provide for preclinical testing of new therapies. The models are divided into two categories. First, genetic models, in which the Nf2 gene is deleted in Schwann cells and as a result animals develop schwannoma tumors. Second, cell transplantation models, mostly orthotopic, in which tumor cells are injected into the cerebellopontine angle, sciatic nerve, or subarachnoid space of the animal, and tumor size is then monitored. Both types of models have been successfully used for preclinical testing of new compounds. The basis and use of such models, together with their relative advantages and disadvantages, will be discussed in this chapter.