Targeting Glioblastoma: Mechanisms of Pathology and Novel Therapeutic Strategies

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About this Research Topic

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Background

Neoplasms of glial cells constitute about 40-50% of the tumors that arise in the central nervous system. Glioblastoma (GBM) is considered one of the most abundant types of glial tumors, with poor prognosis of survival. Recent findings confirm that various factors contribute to the complex pathophysiology of GBM. These include genetic (as well as epigenetic) regulation of carcinogenesis, occurrence of glioma stem-like cells (GSCs) in the tumor mass, or limited permeability of the blood-brain barrier. These factors may be the key obstacles to overcome when designing potentially effective anti-glioblastoma agents. Therefore, the identification of molecular mechanisms involved in the oncogenesis and progression of GBM is essential for the determination of novel strategies in the diagnosis and treatment of this malignancy.

To date numerous advances have been made in understanding the pathophysiology of gliomas. In addition to the well-known prognostic markers of GBM (such as IDH, EGFR, p53, PI3K, Rb and RAF), several novel molecular markers have been proposed as prognostic predictors for patients. Thus, the determination of the methylation status of the O6-methylguanine methyltransferase (MGMT) gene and the discovery of GSCs present considerable clinical relevance. Epigenetic silencing of the MGMT promoter has been identified as a predictive biomarker for the response to the chemotherapy with alkylating agents such as temozolomide. However, despite rapidly increasing knowledge of the biology of GBM and decades of technological advances in neurosurgery, radiotherapy and clinical trials of conventional and novel pharmacological agents, little improvement in the median survival rate of GBM patients has been achieved. Hence, it is essential to improve our current knowledge of the molecular and cellular mechanisms of GBM initiation, progression, and resistance to therapy, and focus on new possible pharmacological agents and drug-delivery systems to defeat this malignancy.

This Research Topic will focus on new advances in the pathophysiology of GBM and its relationship with the normal brain cells and the immune system, as well as novel strategies to overcome treatment resistance and eradicate this deadly brain cancer. Authors are invited to submit Original Research, Review articles and Short Communications covering all aspects of glioblastoma pathophysiology and diagnosis, as well as novel and emerging pharmacotherapeutical approaches to GBM treatment. We welcome submissions covering, but not limited to, the following topics:

• Genetic and epigenetic mechanisms of gliomagenesis
• Chemo- and radiotherapy
• Glioma stem-like cells
• Pharmaceutical nanotechnology
• Immunotherapy
• Epigenetic modifiers
• Natural compounds

Keywords: glioblastoma, pharmacotherapy, diagnosis, nanotechnology, stem-like cells

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