Fig. 6

RHPS4 inhibits glioblastoma cell proliferation through a differential targeting of bulky differentiated- and cancer stem-like cells. RHPS4 differently targets differentiated and GSCs cells. Differentiated glioblastoma cells (white circles) are radiosensitized (white circles marked with plus symbol) through the induction of telomere damage and dysfunctionalization [16, 17]. On the other hand, in GSCs (green circles) RHPS4 strongly reduces CHK1 and RAD51 protein levels leading to S-phase blockage, inhibition of cell proliferation (orange circles) and very likely to cell death. The subsequent exposure to IR determines the cell killing of differentiated (radiosensitized) cells and contributes to the tumor debulking. This model fits very well with data obtained in vivo, indicating that RHPS4 and IR combined treatment avoids tumor relapse and reduce tumor mass also in case of full blown and well-rooted tumors