Cell biology of glioblastoma multiforme: from basic science to diagnosis and treatment

First described in the 1800s, glioblastoma multiforme (GBM), a class IV neoplasm with astrocytic differentiation, as per the revised 2016 World Health Organization classification of tumors of the central nervous system (CNS) is the most common malignant tumor of the CNS. GBM has an extremely wide set of alterations, both genetic and epigenetic, which yield a great number of mutation subgroups, some of which have an established role in independent patient survival and treatment response. All of those components not only represent a closed cycle but are also relevant to the tumor biological behavior and resistance to treatment as they form the pathobiological behavior and clinical course. The presence of different triggering mutations on the background of the presence of key mutations in the GBM stem cells (GBMsc) further separates GBM as primary arising de novo from neural stem cell precursors developing into GBMsc and secondary, by means of aggregated mutations. Some of the change in cellular biology in GBM can be observed via light microscope as they form the cellular and tissue hallmarks of the condition. Changes in genetic information, resulting in alteration, suppression and expression of genes compared to their physiological levels in healthy astrocytes lead to not only cellular, but also extracellular matrix reorganization. These changes result in a multiform number of micromorphological and purely immunological/ biochemical forms. Therefore, in the twenty-first century the term multiforme, previously outcast from nomenclatures, has gained new popularity on the background of genotypic diversity in this neoplastic entry.