The Pivotal Role of Irradiation-induced Autophagy Mechanisms in Glioma Therapy.

Abstract

Glioma epitomizes exclusively primary brain cancer of glial cell or neuroepithelial derivation and irradiation (IR) is one of the key and standard treatment modalities for all kinds of gliomas. Patients with glioma often undergo IR, such as whole-brain radiotherapy, stereotactic radiosurgery, as well as intensity modulated radiation therapy. However, IR therapy for malignant glioma is still facing severe hindrances because gliomas have high resistance to the IR. Autophagy is a type II programmed cell death which has been implicated in IR to gliomas. Autophagy was able to protect cells under sublethal damage circumstances, and it differentially triggered cell death after lethal damage in glioma. Furthermore, IR induced cerebral vascular damage was associated with progressive endothelial cells loss. IR triggered the acceleration of autophagic flux in cerebral endothelial cells which was characterized with robust upregulation of autophagy genes. Thus, autophagy plays a pivotal role in modulating the sensitivity and resistance of glioma cells to IR therapy. However, the exact autophagic mechanisms underlying radiosensitivity and/or radioresistance is still a matter of debate, and the development of effective radiosensitizers are lacking. Specific conditions pointing to the capabilities of IR-induced autophagy augmentation or inhibition of IR-induced cell death mostly contribute to radiosensitivity or radioresistance. Thus, IRinduced autophagy mechanisms in gliomas therapy are multiplex and they either induce radiosensitivity or inhibit radioresistance leading to potential effective treatment strategies for glioma. The aim of this review is to elucidate the autophagic mechanisms associated with radiosensitivity and/or radioresistance in glioma at the bench level, and accordingly highlight the development of potentially effective and efficient radiosensitizers to argument the treatment of glioma.