Molecular Pathogenesis of Vestibular Schwannomas: Insights for the Development of Novel Medical Therapies
Journal Title: Otolaryngologia Polska - Year 2012, Vol 66, Issue 2
Abstract
SUMMARY Vestibular schwannomas (VS), benign intracranial tumors originating from the vestibulocochlear nerve, usually present with hearing loss, tinnitus, and balance dysfunction. Rarely, however, if untreated, these neoplasms can cause significant patient compromise — resulting in facial paralysis, brainstem compression, and even death. Those with vestibular schwannomas currently choose between surgery and stereotactic radiation therapy as available treatment options. Unfortunately, no medical therapies are presently U.S. Food & Drug Administration approved, representing an urgent and unmet clinical need. Recent breakthroughs in research have discovered key celt surface receptors and intracellular signaling pathways that drive vestibular schwannoma tumorigenesis, proliferation, and survival. A number of promising inhibitors targeting these signaling molecules have also now shown efficacy in preclinical VS cell culture models and animal experiments, with some recently entering human clinical trials. In this review, we summarize ErbB receptor signaling, PDGF receptors, MAP kinase signaling, AKT, p21-activated kinase signaling, mTOR, and VEGF signaling in the context of vestibular schwannoma drug development efforts worldwide. Today, it is truly an exciting time as our specialty stands on the verge of major breakthroughs in the development of medical therapies for VS.
Authors and Affiliations
Craig Miller, Suzu Igarashi, Abraham Jacob
Keywords
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