Understanding the Radiobiology of Vestibular Schwannomas to Overcome Radiation Resistance

SIMPLE SUMMARY: Vestibular 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. ABSTRACT: 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.