Abstract
Glioblastoma (GBM) is one of the most aggressive and lethal human brain tumors. At present, GBMs are divided in primary and secondary on the basis of the mutational status of the isocitrate dehydrogenase (IDH) genes. In addition, IDH1 and IDH2 mutations are considered crucial to better define the prognosis. Although primary and secondary GBMs are histologically indistinguishable, they retain distinct genetic alterations that account for different evolution of the tumor. The high invasiveness, the propensity to disperse throughout the brain parenchyma, and the elevated vascularity make these tumors extremely recidivist, resulting in a short patient median survival even after surgical resection and chemoradiotherapy. Furthermore, GBM is considered an immunologically cold tumor. Several studies highlight a highly immunosuppressive tumor microenvironment that promotes recurrence and poor prognosis. Deeper insight into the tumor immune microenvironment, together with the recent discovery of a conventional lymphatic system in the central nervous system (CNS), led to new immunotherapeutic strategies. In the last two decades, experimental evidence from different groups proved the existence of cancer stem cells (CSCs), also known as tumor-initiating cells, that may play an active role in tumor development and progression. Recent findings also indicated the presence of highly infiltrative CSCs in the peritumoral region of GBM. This region appears to play a key role in tumor growing and recurrence. However, until recently, few studies investigated the biomolecular characteristics of the peritumoral tissue. The aim of this review is to recapitulate the pathological features of GBM and of the peritumoral region associated with progression and recurrence.
Highlights
IntroductionDespite the growing experimental investigation in this field and the improved therapeutic strategies, GBM remains essentially incurable, with an overall survival time ranging from 12 to 18 months [3], as less than 5% of patients survive longer than five years after diagnosis [4,5]
GBM is the most common malignant primary brain cancer [1,2]
Among the first microRNAs reported to be overexpressed in GBM compared to the normal brain tissue is miR-21, whose main function is to prevent the activation of the caspase-dependent apoptotic pathway [80], contributing to the onset of the malignant phenotype
Summary
Despite the growing experimental investigation in this field and the improved therapeutic strategies, GBM remains essentially incurable, with an overall survival time ranging from 12 to 18 months [3], as less than 5% of patients survive longer than five years after diagnosis [4,5]. The majority of studies over the years focused on the core tumor area of GBM, whereas less is known about the peritumoral area that may be infiltrated by tumor cells. Recent studies focused on the characterization of this, at first glance, “normal tissue”. This work aims at reviewing recent findings on both the morphological and molecular characterization of GBM and its surrounding tissue, including the presence and the role played by cancer stem cells (CSCs)
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