Pathological and Molecular Features of Glioblastoma and Its Peritumoral Tissue

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.

Novel Treatment Strategies for Glioblastoma

“…Traditionally, the brain is considered an immune-privileged organ due to the existence of the blood brain barrier (BBB) and the absence of a lymphatic drainage system. However, anti-tumor immune responses have been observed in brain tumors [ 59 ], which are proposed to be facilitated by the presence of a lymphatic system [ 60 ]. In general, immunotherapy has been more successful in treating tumors with a high mutational burden [ 61 ], but GBM has a low tumor mutational burden, while also displaying an immunosuppressive environment [ 62 ], and the added complication that chemotherapeutics can also promote an immunosuppressive effect [ 63 ].…”

The Botanical Drug PBI-05204, a Supercritical CO2 Extract of Nerium Oleander, Inhibits Growth of Human Glioblastoma, Reduces Akt/mTOR Activities, and Modulates GSC Cell-Renewal Properties

“…Total neurosurgical resection is possible only when patients are diagnosed early. Lack of neurosurgical removal of tumor is a major cause for poor prognosis for adult patient with GBM with a 5-year survival rate of less than 5% (D'Alessio et al, 2019). Failure of standard of care chemo/radiotherapy regimens has been attributed to a number of factors such as tumor microenvironment, de novo and/or acquired tumor resistance, poor drug delivery, further angiogenesis and/or vasculogenic mimicry (VM), and/or the facile emergence of glioma stem cells (GSCs) (Yan et al, 2016;Mooney et al, 2019;Yan et al, 2019a;Yan et al, 2019b).…”

Giant cell glioblastoma is a distinctive subtype of glioma characterized by vulnerability to DNA damage

“…To compere the protective function against DNA damage in GC-GBM and MS-GBM, we studied the expression of stem cell markers, because some have been shown to function against DNA damage. To detect stem cells in GBM, many types of markers have been reported [17,18]. Among markers stained in the present study, PODXL [19] showed a propensity for small cells around vessels (Cases 3 and 5) and in palisading areas (Case 10) (Fig.…”