Emerging Treatment of Glioblastoma Multiforme

Dear Colleagues,

Glioblastoma multiforme (GBM) is one of the most aggressive tumors of the brain and, despite the continuous research developed over the last few decades, the prognosis for patients remains extremely poor. The current standard of care, the so-called Stupp protocol, includes surgery, radiotherapy, and chemotherapy, typically using the alkylating agent temozolomide (TMZ). The significant tumor heterogeneity of GBM promotes the selection of resistant subpopulations, leading to tumor recurrence and thus the universally lethal outcome. Moreover, the presence of a population of stem-like cells, the glioma stem cells (GSCs), characterized by the ability of self-renewal and tumorigenicity, contribute to therapy resistance, which remains a significant challenge to overcome. Furthermore, GBM creates a highly immunosuppressive environment with multiple mechanisms of immune evasion, preventing the effective functioning of various immunotherapy approaches. Indeed, phase III clinical studies with immune checkpoint inhibitors and vaccine therapy have been, thus far, disappointing. Remarkably, one crucial obstacle to effective treatment is the blood–brain barrier (BBB), which protects the CNS from environmental toxins, and the difficulty that some therapies have in passing the BBB. The drugs currently in use (chemotherapy drugs, immunotherapy or monoclonal antibodies) are all subject to perfusion differences in tumor vessels, resulting in different drug concentrations in various sites, which affects their clinical efficacy. Given that the currently approved treatments for GBM have largely been inadequate, new therapeutic strategies are urgently needed. This Special Issue aims to collect studies on existing and emerging therapies, including clinical trials, with a particular emphasis on the following topics:

• Drug delivery technologies;
• Cell delivery systems;
• Radiosurgical techniques;
• Adjuvants therapies;
• Techniques to overcome the blood–brain barrier (BBB);
• Gene therapy;
• GSCs-targeting therapies;
• Nanomedicine and nanotechnologies;
• Potential GBM small-molecule inhibitors;
• Immunotherapy (immune checkpoint blockade, chimeric antigen receptor T (CAR T) cell therapy, oncolytic virotherapy, and vaccine therapy).

Dr. Cristina Pagano
Guest Editor

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• glioblastoma
• emerging therapies
• drug delivery
• immunotherapy
• nanomedicine
• radiotherapy
• viral therapy