Understanding glioma stem cells: rationale, clinical relevance and therapeutic strategies

Glioblastoma multiforme is one of the most aggressive brain tumors in adults. Despite the use of the best available multimodal therapeutic approaches, the prognosis remains dismal. The identification of glioma stem cells (GSCs) has offered new hope to affected patients, since it could explain, in part, the highly heterogeneous nature of this tumor and its chemo- and radioresistance. Although still in its infancy, GSC research has unveiled many of its complexities and the theory itself remains controversial. GSC phenotype can significantly vary between patients and a single tumor may present several distinct GSCs. New therapeutic solutions that effectively target this population are of utmost importance, since they may be able to decrease neoplastic recurrence and improve patient survival. Here, we discuss the mechanisms by which GSCs lead to glioma relapse, the main controversies in this field and the most recent treatments that could successfully target this population.