Understanding the Radiobiology of Vestibular Schwannomas to Overcome Radiation Resistance

Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8–10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance.

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Radiobiology of vestibular schwannomas: mechanisms of radioresistance and potential targets for therapeutic sensitization

Neurosurgical FOCUS ◽

10.3171/2009.9.focus09185 ◽

2009 ◽

Vol 27 (6) ◽

pp. E2 ◽

Cited By ~ 24

Author(s):

Andrea H. Yeung ◽

Michael E. Sughrue ◽

Ari J. Kane ◽

Tarik Tihan ◽

Steven W. Cheung ◽

...

Keyword(s):

Radiation Treatment ◽

Molecular Level ◽

Vestibular Schwannomas ◽

Benign Tumors ◽

Tumor Control ◽

Side Effect Profile ◽

Novel Therapies ◽

Microsurgical Resection ◽

Selection For ◽

Cranial Nerve Viii

Vestibular schwannomas (VS) are benign tumors arising from the Schwann cells of cranial nerve VIII. Historically the prevailing therapy for patients with VS has been microsurgical resection. More recently, stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy have gained acceptance as effective alternatives. Although the side effect profile and rates of tumor control appear to be favorable for SRS, there is a subset of radioresistant tumors that continue to progress despite properly administered radiation treatment. In this review, the authors summarize what is known about the mechanism of radioresistance in VS at the clinical and molecular level. An improved understanding of the radiobiological behavior of VS may help guide appropriate patient selection for SRS and potentially aid in the design of novel therapies to treat radioresistant tumors.

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Molecular biology of sporadic vestibular schwannomas including genetic and epigenetic alterations

Polski Przegląd Otorynolaryngologiczny ◽

10.5604/01.3001.0014.4201 ◽

2020 ◽

Vol 9 (3) ◽

pp. 23-29

Author(s):

Maria Makuszewska ◽

Małgorzata Litwiniuk-Kosmala ◽

Robert Bartoszewicz ◽

Kazimierz Niemczyk

Keyword(s):

Molecular Biology ◽

Current Knowledge ◽

Expression Profiles ◽

Neurofibromatosis Type ◽

Nerve Fibers ◽

Vestibular Schwannomas ◽

Benign Tumors ◽

Slow Growth Rate ◽

Brainstem Compression ◽

Altered Gene

Introduction: Vestibular schwannomas (VSs) are benign tumors, developing from neoplastic Schwann cells, that produce myelin sheath covering vestibular nerve fibers. The majority of these tumors are sporadic VS and very rarely they can be associated with neurofibromatosis type 2 (NF2). VSs are usually characterized with slow growth rate, however some of them appear to have a cystic structure, grow more rapidly, can cause facial nerve palsy and brainstem compression. The molecular hallmark of both sporadic and NF-2 associated VS is the inactivation of supresor gene NF-2, also called merlin gene. Aim: In this review we summarize the current knowledge on the molecular biology of VS, including genetic and epigenetic aberrations, altered gene expression and specific microRNA expression profiles.

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Molecular biology of familial and sporadic vestibular schwannomas: implications for novel therapeutics

Journal of Neurosurgery ◽

10.3171/2009.10.jns091135 ◽

2011 ◽

Vol 114 (2) ◽

pp. 359-366 ◽

Cited By ~ 28

Author(s):

Michael E. Sughrue ◽

Andrea H. Yeung ◽

Martin J. Rutkowski ◽

Steven W. Cheung ◽

Andrew T. Parsa

Keyword(s):

Molecular Biology ◽

Cranial Nerve ◽

Single Gene ◽

Vestibular Schwannomas ◽

Benign Tumors ◽

Genetic Mutations ◽

Chromosome 22 ◽

Novel Therapeutics ◽

Broad Variety ◽

Cranial Nerve Viii

Vestibular schwannomas (VSs) are benign tumors arising from the sheath of cranial nerve VIII. The pathogenesis underlying most familial and sporadic VSs has been linked to a mutation in a single gene, the neurofibromin 2 (NF2) gene located on chromosome 22, band q11–13.1. In this review, the authors summarized what is known about the epidemiology of NF2 mutations and patients with VSs. The authors also discuss the function of the NF2 gene product, merlin, and describe the known and hypothetical effects of genetic mutations that lead to merlin dysfunction on a broad variety of cellular and histological end points. A better understanding of the molecular pathobiology of VSs may lead to novel therapeutics to augment current modalities of treatment while minimizing morbidity.

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Microsurgical Resection of Vestibular Schwannomas, Presentation of Cases in 3D: 3-Dimensional Operative Video

Operative Neurosurgery ◽

10.1093/ons/opz271 ◽

2019 ◽

Vol 19 (1) ◽

pp. E61-E62

Author(s):

Alvaro Campero ◽

Matias Baldoncini

Keyword(s):

Facial Nerve ◽

Cochlear Nerve ◽

Vestibular Schwannomas ◽

Benign Tumors ◽

3 Dimensional ◽

Microsurgical Resection ◽

Magnetic Resonance Imaging Mri ◽

The Right ◽

Functional Preservation

Abstract Vestibular schwannomas are the most common benign tumors of the pontocerebellar angle,1,2 their microsurgical complexity is related to their size and neurovascular relationships. The purpose of this work is to analyze the clinical, anatomic characteristics, microsurgical treatment, and the postoperative results according to the Hannover gradual scale in 4 patients with vestibular schwannomas. The 4 patients gave their consent to the procedure and all consented to the use of their surgical videos, preoperative and postoperative studies, and postoperative pictures. Case 1: A 39-yr-old woman, with left ear hearing loss. Magnetic resonance imaging (MRI) showed small Intracanalicular schwannoma (T1 classification by Hannover). Microsurgery was performed and resection through a retrosigmoid approach2,3 with anatomic and functional preservation of the facial and cochlear nerve. Case 2: A 40-yr-old woman, with left ear hypoacusia. MRI showed an extrameatal schwannoma reaching the brainstem (T3b Hannover classification). The complete re-section through retrosigmoid approach were performed. Case 3: A 69-yr-old woman, without hearing in the right ear. RM: Medium schwannoma (T4a classification of Hannover). Microsurgery was performed with anatomic and functional preservation of the facial nerve.4-6 Case 4: A 32-yr-old woman, without hearing in the left ear. In addition, cerebellar syndrome and headache. RM: Large schwannoma (T4b classification of Hannover). Sur-gery was performed, anatomic preservation of the facial nerve, with moderate paresis in the postoperative period. Microsurgical resection with functional preservation of the facial and cochlear nerve is the main objective7 when addressing this pathology.

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