The Role of Autophagy in Brain Tumors

Primary and metastatic brain tumors are among the most threatening diseases world- wide. Even improved surgical interventions often cannot completely eradicate brain tumors that progress and metastasize, reducing the patient’s chance of survival. Current therapeutic options, such as radio- and chemotherapies, as well as immunotherapy, are also ineffective because brain tumors are highly resistant to therapies. Autophagy is a highly conserved cellular homeostatic process that maintains cellular homeostasis through the degradation, elimination, and recycling of damaged substrates, such as organelles, macromolecules, and misfolded proteins. However, its deregulation is associated with several pathological processes, including cancer. It has been demonstrated that au- tophagy has a double role, both as a tumor promoter and as a suppressor. It promotes cancer initiation and survival through the recycling of intracellular substrates in order to sustain tumor metabolism, contributing to the acquisition of resistance to treatments; and it inhibits cancer progression by removing damaged proteins and organelles, in order to protect cells from reactive oxygen species (ROS), inflammation, necrosis, and other causes of genomic instability. Therefore, autophagy manipulation could be a novel anticancer strategy exploited to improve the outcome of cancer treatments, including brain tumors, as shown in this series of five articles (one review and four articles).