Dual perspective on autophagy in glioma: Detangling the dichotomous mechanisms of signaling pathways for therapeutic insights

Autophagy is a normal physiological process that aids the recycling of cellular nutrients, assisting the cells to cope with stressed conditions. However, autophagy's effect on cancer, including glioma, is uncertain and involves complicated molecular mechanisms. Several contradictory reports indicate that autophagy may promote or suppress glioma growth and progression. Autophagy inhibitors potentiate the efficacy of chemotherapy or radiation therapy in glioma. Numerous compounds stimulate autophagy to cause glioma cell death. Autophagy is also involved in the therapeutic resistance of glioma. This review article aims to detangle the complicated molecular mechanism of autophagy to provide a better perception of the two-sided role of autophagy in glioma and its therapeutic implications. The protein and epigenetic modulators of the cytoprotective and cytotoxic role of autophagy are described in this article. Moreover, several signaling pathways are associated with autophagy and its effects on glioma. We have reviewed the molecular pathways and highlighted the signaling axis involved in cytoprotective and cytotoxic autophagy. Additionally, this article discusses the role of autophagy in therapeutic resistance, including glioma stem cell maintenance and tumor microenvironment regulation. It also summarizes several investigations on the anti-glioma effects of autophagy modulators to understand the associated mechanisms and provide insights regarding its therapeutic implications.