Autophagy in Human Brain Cancer

Autophagy is a physiological process, evolutionarily conserved, able to preserve cells from both endogenous and environmental threats. Baseline autophagy contributes to the maintenance of cellular homeostasis, and autophagic flow is upregulated in response to many adverse conditions, including nutrient or growth factor deprivation, accumulation of unfolded proteins, and intracellular infection. Although autophagy frequently exerts cytoprotective functions by acting as a stress response mechanism, in some settings, it may contribute to the execution of cell death, representing the type 2 programmed cell death. Moreover, autophagy drives key processes in cancer, including glioblastoma (the most frequent and malignant brain tumor in adults). An effective autophagy function may protect cells against the consequences of gene mutation and altered signal pathways leading to tumor initiation, promotion, and progression toward highly aggressive behaviors, such as enhanced proliferation, infiltration, and metastases. Moreover, autophagy activation has been extensively reported as able to modulate effectiveness of current anticancer agents, such as chemotherapy, ionizing radiation, target therapy, and immunotherapy. However, its role as a prosurvival or prodeath cellular process is still debated. In this chapter, emerging results from scientific literature are reported, describing in vitro, in vivo, and preclinical evidence of autophagy involvement in glioblastoma. The chapter also describes how the autophagy process can switch to apoptosis (type 1 programmed cell death) or how it can be modulated by microRNA (small noncoding RNA molecules that regulate protein expression by cleaving or repressing the translation of target mRNAs). In conclusion, the autophagy process plays a crucial role not only in tumor development, progression, and malignancy, but also in modulating the current therapy, providing new encouraging strategies for tumor treatmen