Molecular pathogenesis of vestibular schwannomas: Insights for the development of novel medical therapies

Craig Miller, Suzu Igarashi, Abraham Jacob

Research output: Contribution to journalEditorial

2 Scopus citations

Abstract

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 cell 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.

Original languageEnglish (US)
Pages (from-to)84-95
Number of pages12
JournalOtolaryngologia Polska
Volume66
Issue number2
DOIs
StatePublished - Jan 1 2012

Keywords

  • AKT
  • EGFR
  • Merlin
  • NF2
  • Neurofibromatosis type 2
  • PAK
  • PDGF
  • VEGF
  • Vestibular Schwannoma

ASJC Scopus subject areas

  • Otorhinolaryngology

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