Figure 1. ALK inhibitors inhibit or partially inhibit the proliferation of neuroblastoma cell lines harboring ALK aberrations.
(A) Dose response curves of ALK-amplified or ALK mutant neuroblastoma cell lines exposed to the ALK inhibitors ceritinib, crizotinib, alectinib and PF06463922. Relative cell growth was quantified using CellTiter-Glo on day 6. Data are shown as mean ± SEM from three biological replicates. (B) IC50 values of ceritinib, crizotinib, alectinib and PF06463922 across Ba/F3 cells expressing wild-type or F1174L-mutated EML4-ALK and neuroblastoma cell lines harboring ALK aberrations. The data of Ba/F3 cells were reported by Zou and colleagues (28). (C) Inhibition of ALK autophosphorylation and downstream signaling by ceritinib, crizotinib and PF06463922 in ALK-amplified or ALK mutant neuroblastoma cell lines. Cells were harvested after treatment for 4 hr with the indicated compounds at different concentrations. Whole cell lysates were analyzed by Western blotting to detect the levels of ALK, AKT and ERK proteins and their phosphorylation.