The IL13α 2R paves the way for anti-glioma nanotherapy.

Glioblastoma (GBM) is one of the most aggressive (grade IV) gliomas characterized by a high rate of recurrence, resistance to therapy and a grim survival prognosis. The long-awaited improvement in GBM patients' survival rates essentially depends on advances in the development of new therapeutic approaches. Recent preclinical studies show that nanoscale materials could greatly contribute to the improvement of diagnosis and management of brain cancers. In the current review, we will discuss how specific features of glioma pathobiology can be employed for designing efficient targeting approaches. Moreover, we will summarize the main evidence for the potential of the IL-13R alpha 2 receptor (IL13α2R) targeting in GBM early diagnosis and experimental therapy.

The Role of the Metabolism of Zinc and Manganese Ions in Human Cancerogenesis.

Metal ion homeostasis is fundamental for life. Specifically, transition metals iron, manganese and zinc play a pivotal role in mitochondrial metabolism and energy generation, anti-oxidation defense, transcriptional regulation and the immune response. The misregulation of expression or mutations in ion carriers and the corresponding changes in Mn2+ and Zn2+ levels suggest that these ions play a pivotal role in cancer progression. Moreover, coordinated changes in Mn2+ and Zn2+ ion carriers have been detected, suggesting that particular mechanisms influenced by both ions might be required for the growth of cancer cells, metastasis and immune evasion. Here, we present a review of zinc and manganese pathophysiology suggesting that these ions might cooperatively regulate cancerogenesis. Zn and Mn effects converge on mitochondria-induced apoptosis, transcriptional regulation and the cGAS-STING signaling pathway, mediating the immune response. Both Zn and Mn influence cancer progression and impact treatment efficacy in animal models and clinical trials. We predict that novel strategies targeting the regulation of both Zn and Mn in cancer will complement current therapeutic strategies.

Oncolytic Virus-Induced Autophagy in Glioblastoma.

Autophagy is a catabolic process that allows cells to scavenge damaged organelles and produces energy to maintain cellular homeostasis. It is also an effective defense method for cells, which allows them to identify an internalized pathogen and destroy it through the fusion of the autophagosome and lysosomes. Recent reports have demonstrated that various chemotherapeutic agents and viral gene therapeutic vehicles provide therapeutic advantages for patients with glioblastoma as monotherapy or in combination with standards of care. Despite nonstop efforts to develop effective antiglioma therapeutics, tumor-induced autophagy in some studies manifests tumor resistance and glioma progression. Here, we explore the functional link between autophagy regulation mediated by oncolytic viruses and discuss how intracellular interactions control autophagic signaling in glioblastoma. Autophagy induced by oncolytic viruses plays a dual role in cell death and survival. On the one hand, autophagy stimulation has mostly led to an increase in cytotoxicity mediated by the oncolytic virus, but, on the other hand, autophagy is also activated as a cell defense mechanism against intracellular pathogens and modulates antiviral activity through the induction of ER stress and unfolded protein response (UPR) signaling. Despite the fact that the moment of switch between autophagic prosurvival and prodeath modes remains to be known, in the context of oncolytic virotherapy, cytotoxic autophagy is a crucial mechanism of cancer cell death.