The peritumoral brain zone in glioblastoma: where we are and where we are going

Glioblastoma (GBM) is the most aggressive and invasive primary brain tumor. Current therapies are not curative, and patients' outcomes remain poor with an overall survival of 20.9 months after surgery. The typical growing pattern of GBM develops by infiltrating the surrounding apparent normal brain tissue within which the recurrence is expected to appear in the majority of cases. Thus, in the last decades, an increased interest has developed to investigate the cellular and molecular interactions between GBM and the peritumoral brain zone (PBZ) bordering the tumor tissue. The aim of this review is to provide up-to-date knowledge about the oncogenic properties of the PBZ to highlight possible druggable targets for more effective treatment of GBM by limiting the formation of recurrence, which is almost inevitable in the majority of patients. Starting from the description of the cellular components, passing through the illustration of the molecular profiles, we finally focused on more clinical aspects, represented by imaging and radiological details. The complete picture that emerges from this review could provide new input for future investigations aimed at identifying new effective strategies to eradicate this still incurable tumor.