Fig 6. Model prediction of response and resistance factors.

A: Model overview showing changed rates for EGFR and MMET synthesis, and PI3K mutation. B: In silico screening for MMET expression silencing in Hs746T cell line for unstimulated, EGF, and EGF in combination with cetuximab treatment at 3 min. C: Model prediction and experimental validation of MMET expression silencing using siRNA MET at 3 min. For the simulation, the MMET synthesis rate was scaled with the measured MMET reduction achieved by siRNA treatment in the untreated (no stimulation) condition. D: In silico screening for EGFR expression silencing in MKN1 cell line for unstimulated, EGF, and EGF in combination with cetuximab treatment at 5 min. For the simulation, the EGFR synthesis rate was scaled with the measured EGFR reduction achieved by siRNA treatment in the untreated (no stimulation) condition. E: Model prediction and experimental validation of EGFR expression silencing using siRNA EGFR at 5 min. F: Model prediction of time response of AREG stimulation (black line) shows higher sensitivity to cetuximab treatment compared to EGF (red line) in MKN1 cells. B-F: The signal is normalized with respect to the maximum activity level for each observed component. Western blot images corresponding to C and E are provided in S11 and S12 Figs.