Autophagy machinery in glioblastoma: The prospect of cell death crosstalk and drug resistance with bioinformatics analysis

Brain tumors are common malignancies with high mortality and morbidity in which glioblastoma (GB) is a grade IV astrocytoma with heterogeneous nature. The conventional therapeutics for the GB mainly include surgery and chemotherapy, however their efficacy has been compromised due to the aggressiveness of tumor cells. The dysregulation of cell death mechanisms, especially autophagy has been reported as a factor causing difficulties in cancer therapy. As a mechanism contributing to cell homeostasis, the autophagy process is hijacked by tumor cells for the purpose of aggravating cancer progression and drug resistance. The autophagy function is context-dependent and its role can be lethal or protective in cancer. The aim of the current paper is to highlight the role of autophagy in the regulation of GB progression. The cytotoxic function of autophagy can promote apoptosis and ferroptosis in GB cells and vice versa. Autophagy dysregulation can cause drug resistance and radioresistance in GB. Moreover, stemness can be regulated by autophagy and overall growth as well as metastasis are affected by autophagy. The various interventions including administration of synthetic/natural products and nanoplatforms can target autophagy. Therefore, autophagy can act as a promising target in GB therapy.