Brain diseases come in many different forms. It is estimated that these pathologies affect the lives of 1 in 6 people, and cost over a trillion dollars in annual treatment. The major categories of brain diseases include diverse brain cancers. Brain tumors are the most primitive, invasive and malignant in humans with poor survival after diagnosis (Mckinney, 2004; Laquintana et al., 2009). Although in recent years, numerous studies have been carried out to identify novel therapeutic protocols and tumor molecular markers capable to predict survival and response to treatment, the life expectancy of neuro-oncological patients is still very limited (24–36 months)(Aldape et al., 2019; Liang et al., 2020).

About 33% of all brain tumors are gliomas, accounting for about 80% of the total malignant central nervous system (CNS) tumors in adults (Hanif et al., 2017). Glioma is a broad category of glial brain and spinal cord tumors which originate in the glial cells that surround and support neurons in the brain, including astrocytes, oligodendrocytes, and ependymal cells. Among these, glioblastoma (GBM) is one of the most common and aggressive primary brain tumors (van Tellingen et al., 2015; Davis, 2016; Taylor et al., 2019; Birzu et al., 2021), characterized by diffuse infiltration of the adjacent brain parenchyma and development of drug resistance to standard treatment (Chen et al., 2018; Shergalis et al., 2018). So far, GBM remains associated with an extremely aggressive clinical course, and only 0.05–4.7% of patients survive 5 years from diagnosis (Ostrom et al., 2018). Cellular pleomorphism with nuclear atypia, high mitotic activity, and microvascular proliferation distinguish GBM from other lower-grade gliomas (Hambardzumyan and Bergers, 2015). In addition, the inter-and intra-patient tumor heterogeneity causes several obstacles, limiting the improvement of an early diagnosis and treatment protocols.