Figure 1. Resistance to Ras targeted therapies is rapidly induced and results in stable rewiring of Ras effector pathways.

(A) Representative plots including technical replicate data points of drug responses in resistant vs naïve NCI-H358 cells. (B) Acute treatments of naïve cells with IC₉₀ concentrations of inhibitor re-dosed every 48 h results in rapid re-activation of Ras effectors. Where re-dosing or cell harvesting occurred on the same day, e.g. 4 days, cells harvested at day 4 will have been re-dosed 48 h previously. High levels of Ras pathway activation are maintained in resistant cells even after drug washout with vehicle. (−) cells treated with vehicle control, (R) resistant NCI-H358 cells continuously cultured for at least 30 days in the presence of drug, (N) naïve NCI-H358 cells. Blots are representative of n = 3 biological repeats.