Drug screens using tumorspheres and fresh tumor cells from G3MB and SHHMB PDX. A, Drug-screening strategy using tumorspheres (HD-MB03) and fresh tumor cells dissociated from intracranial PDXs (MB002, SJMBG3–12–5950, SJMBG3–16–08522, SJMBSHH-13–5634, and SJMBSHH-14–7196). Synergistic and additive combinations tested in preclinical trials using G3MB and SHHMB PDX-bearing mice. B, Approximation of the number of cell divisions of untreated cells during 7 days of incubation in 384-well plates. CellTiter Glo reagent used on untreated cells on days 0 and 7. RLU fold change computed and log2 transformed. 1,000 cells per well density for all models (n = 3–7). C, The IC50 heatmap of the 87 drugs assayed as single agent in the different cell models after 7 days of treatment (n = 3 and technical duplicate or triplicate for each). * Compounds used in vivo identified with a red star. Raw data are presented in Supplementary Table S1.