Abstract
Simple SummaryVestibular schwannomas (VS) are intracranial tumors that originate from the Schwann cells of the vestibulocochlear nerve and cause hearing loss and dizziness. Although radiation therapy is a common treatment for VS, some irradiated tumors do not respond well and continue to grow, requiring additional therapies such as surgery. Little is known about the molecular mechanisms behind the normal response of VS to radiation therapy and why some VS are resistant to radiation. Thus, we aimed to review the current understanding of radiation response and resistance in VS through an in-depth summary of the DNA damage and cell cycle response to ionizing radiation. A better understanding of the radiobiology of VS can help guide future investigations looking at optimal radiation dosing strategies, unique targets for intervention, and novel therapies to improve patient outcomes.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.
Highlights
Vestibular schwannomas (VS) are benign intracranial tumors that arise from the vestibulocochlear nerves
When double-stranded breaks (DSBs) are present in the G1 phase of the cell cycle, MRE11 and NBS1 detect the DSB, MRE11 induces autophosphorylation and monomerization of the ataxia telangiectasia mutated (ATM) kinase, and ATM kinase stabilizes tumor protein 53 (p53), which leads to cell cycle arrest [55]
We focus primarily on homologous recombination (HR) and nonhomologous end joining (NHEJ), since they are the primary mechanisms of DNA repair following the development of DSBs after ionizing radiation (IR) [67,68]
Summary
Vestibular schwannomas (VS) are benign intracranial tumors that arise from the vestibulocochlear nerves. In a meta-analysis of 2109 patients that received observation as the initial treatment, the local control rate was found to be 65% (95% Confidence Interval (CI): 55.9%, 73.6%) at the end of follow-up treatment (median: 3.4 years). The tumor control rate after single fraction SRS in growing VS has been reported to be approximately 77% at 10 years [30]. With single fraction SRS, published long-term tumor control rates for NF2-associated VS are about 84–87% [34,35,36]; the tumor control rate declines to about 40% for NF2 patients in some studies depending on the initial tumor size treated, the radiation protocol used, and whether the tumor was growing at the time of radiation [32,37]. We summarize current knowledge regarding the effects of radiation on VS cells and describe future directions of research that can potentially improve clinical outcomes after radiation in VS patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
