Vestibular schwannomas are histopathologically benign
tumors arising from the Schwann cell sheath surrounding the vestibular branch of cranial nerve VIII and are related to the NF2 gene and its product
merlin.
Merlin acts as a
tumor suppressor and as a mediator of contact inhibition. Thus, deficiencies in both NF2 genes lead to
vestibular schwannoma development. Recently, there have been major advances in our knowledge of the molecular biology of
vestibular schwannomas as well as the development of novel
therapies for its treatment. In this article the authors comprehensively review the recent advances in the molecular biology and characterization of
vestibular schwannomas as well as the development of modern treatments for
vestibular schwannoma. For instance,
merlin is involved with a number of receptors including the CD44 receptor, EGFR, and signaling pathways, such as the Ras/raf pathway and the canonical Wnt pathway. Recently,
merlin was also shown to interact in the nucleus with
E3 ubiquitin ligase CRL4(DCAF1). A greater understanding of the molecular mechanisms behind
vestibular schwannoma tumorigenesis has begun to yield novel
therapies. Some authors have shown that
Avastin induces regression of progressive
schwannomas by over 40% and improves hearing. An inhibitor of
VEGF synthesis,
PTC299, is currently in Phase II trials as a potential agent to treat
vestibular schwannoma. Furthermore, in vitro studies have shown that
trastuzumab (an ERBB2 inhibitor) reduces
vestibular schwannoma cell proliferation. With further research it may be possible to significantly reduce morbidity and mortality rates by decreasing
tumor burden,
tumor volume,
hearing loss, and cranial nerve deficits seen in
vestibular schwannomas.