Moreover, we propose that CLIC1 is a major determinant of cancer stem cell activity, at least in GBM, controlling not only cell proliferation but also invasiveness and, more in general, tumorigenesis, and that antitumor activity of biguanide-based compounds requires its inhibition, among all the different intracellular mechanisms that these drugs can affect. Here, CLIC1 is linked to glioblastoma.