Fig. 7

NF1 knockout cell line models are sensitive to MEK and pan-RAF inhibitor treatment. a and b Drug screen of NF1 knockout cell lines and ectopic NRAS^Q61K expression models. Cell were treated with trametinib (MEKi), rapamycin (mTORi), pictilisib (GDC0941, PI3Ki) or pan-RAF inhibitor LY3009120 for 72 hours and cell viability assessed using CellTiterGlo measurements. Colors indicate log2(FC) of absolute IC₅₀ values to values of the parental or empty vector control cell lines. Red indicates a higher sensitivity in comparison to the parental cell line or empty vector control and blue a decreased sensitivity. Respective absolute IC₅₀ values are shown for each treatment. c and d Respective concentration-response curves of NF1 knockout clones and ectopic NRAS^Q61K expression models for MEK inhibitor treatment with trametinib; values represent mean ± SD, n = 3. e, f and g Western blot analysis of 24-hour-serum-starved NF1 knockout cell lines, ectopic NRAS^Q61K expression models and NBLW-R resistant models exposed to DMSO, ceritinib, lorlatinib or trametinib for 1 hour with subsequent stimulation for 30 minutes with EGF or PBS. h Schematic of canonical ALK downstream signaling in comparison to signaling in neuroblastoma cell lines with mutated NRAS^Q61K or a NF1 knockout