Subventricular zone microenvironment protects glioblastoma cells from radiotherapy cytotoxicity: role of the chemokine CXCL12

Glioblastoma (GBM) is the most aggressive primary glial tumor in adults and, notwithstanding all the novel treatment approaches to date developed, the outcome remains frustrating poor (1). Indeed, in most cases GBM rapidly relapses also after aggressive multimodal therapy (surgical resection, followed by radiotherapy with concomitant and adjuvant chemotherapy with temozolomide), and the limited benefit of the available treatments at relapse are not able to improve GBM patients’ median overall survival (OS) beyond 15 months (2). However, although current therapeutic approaches have not improved patients’ life expectance, in the recent years significant progresses were obtained in defining the biological features of GBM cells. In particular, in last few years a new paradigm of tumorigenesis has been proposed, in which a small cell population within the tumor mass, the so-called cancer stem cells (CSC), was identified as the main determinant of tumor development, progression, and recurrence (3) and, due to the intrinsic high resistance to chemo- and radio-therapy of these cells, it is now evident that efficient suppression of CSC in GBM [i.e., glioma stem cell (GSC)] represents an absolutely required goal to eradicate the tumor and prevent relapses (4). Therefore, the identification of the molecular determinants involved in the pharmacological resistance of GSC is urgently expected as a new potential targets for innovative and more efficacious therapeutic interventions