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A Unified Methodological Framework for Vestibular Schwannoma Research
Published on: June 20, 2017
A Critical Overview of Targeted Therapies for Vestibular Schwannoma
1Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Abstract:
Vestibular schwannoma (VS) is a benign tumor that originates from Schwann cells in the vestibular component. Surgical treatment for VS has gradually declined over the past few decades, especially for small tumors. Gamma knife radiosurgery has become an accepted treatment for VS, with a high rate of tumor control. For neurofibromatosis type 2 (NF2)-associated VS resistant to radiotherapy, vascular endothelial growth factor (VEGF)-A/VEGF receptor (VEGFR)-targeted therapy (e.g., bevacizumab) may become the first-line therapy. Recently, a clinical trial using a VEGFR1/2 peptide vaccine was also conducted in patients with progressive NF2-associated schwannomas, which was the first immunotherapeutic approach for NF2 patients. Targeted therapies for the gene product of SH3PXD2A-HTRA1 fusion may be effective for sporadic VS. Several protein kinase inhibitors could be supportive to prevent tumor progression because merlin inhibits signaling by tyrosine receptor kinases and the activation of downstream pathways, including the Ras/Raf/MEK/ERK and PI3K/Akt/mTORC1 pathways. Tumor-microenvironment-targeted therapy may be supportive for the mainstays of management. The tumor-associated macrophage is the major component of immunosuppressive cells in schwannomas. Here, we present a critical overview of targeted therapies for VS. Multimodal therapy is required to manage patients with refractory VS.
Insights
Targeted therapies offer new hope for vestibular schwannoma (VS) management, particularly for neurofibromatosis type 2 (NF2) cases. Research explores novel approaches like immunotherapy and targeted agents to improve outcomes for refractory VS.
Area of Science:
- Neuro-oncology
- Oncological therapeutics
- Tumor biology
Background:
- Vestibular schwannoma (VS) is a benign tumor arising from Schwann cells.
- Surgical treatment for VS has decreased, with radiosurgery becoming standard.
- Emerging therapies are needed for radiotherapy-resistant and progressive VS.
Purpose of the Study:
- To provide a critical overview of current and emerging targeted therapies for vestibular schwannoma.
- To highlight novel therapeutic strategies for sporadic and NF2-associated VS.
- To discuss the role of tumor microenvironment modulation in VS management.
Main Methods:
- Review of current literature on vestibular schwannoma treatments.
- Analysis of targeted therapy approaches, including molecular and immunotherapeutic strategies.
- Examination of the role of tumor-associated macrophages and signaling pathways.
Main Results:
- Gamma knife radiosurgery shows high tumor control rates for VS.
- VEGF-targeted therapies (e.g., bevacizumab) show promise for NF2-associated VS.
- Immunotherapy and targeted agents against SH3PXD2A-HTRA1 fusion are under investigation.
- Protein kinase inhibitors and tumor microenvironment modulation are potential supportive strategies.
Conclusions:
- Targeted therapies represent a significant advancement in vestibular schwannoma treatment.
- Multimodal therapeutic approaches are essential for managing refractory VS.
- Future research should focus on personalized and combination therapies for improved patient outcomes.
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