Signalling pathways in Glioblastoma as target for innovative therapy

Glioblastoma (GBM) is an aggressive and invasive brain tumor. The first line treatment usually is the surgical resection, followed by radiotherapy and the administration of the alkylating agent Temozolomide. Significant intra- and inter-tumor heterogeneity have been associated with aberrations in different intracellular pathways and a peculiar tumor microenvironment (TME) that contributes to GBM aggressiveness. In GBM, tumor cells can escape from apoptosis because there is an overexpression of anti-apoptotic proteins and an inhibition of pro-apoptotic ones, like Bax. The tumor progression could be due also to the deregulation of the oncosuppressor protein p53. The overexpression of p53 inhibitor, MDM2, often occurs in GBM promoting its proliferation. The reactivation of p53 endogenous function can represent an important target in the development of effective GBM treatment. The failure of GBM treatment is also due to the presence of a peculiar TME. Tumor cells regulate the function of cellular and non-cellular components through complex signalling pathways and could use the non-malignant cells to work for their benefit. Adenosine is one of the main immunomodulatory mediators involved in tumor development. Herein, we deeply investigated the aberrant intracellular signalling pathways involved in GBM pathogenesis and how the modulation of these pathways could prevent GBM aggressiveness.