Fig. 2: Sensitivity of NSCLC cell lines to KRAS^G12C inhibitors is highly correlated with their inhibition of PI3K-AKT-mTOR signaling.

a Immunoblots of KRAS^G12C mutant cell lines treated with 1 µM AZD8037 for the indicated times. Scattered plot of cell viability for the KRAS^G12C mutant cell lines following 72 h treatment plotted against quantified immunoblot intensities of the indicated phosphorylated protein normalized against the respective total protein after 24 h treatment. The plots show 12 cell lines plotted twice each for independent experiments with either 1 µM Sotorasib or 1 µM AZD8037. R² calculated by linear regression. c Same as (b) but with 12 cell lines plotted once each after treatment with 100 nM RM-018. d Cell viability as percentage change from control of KRAS^G12C mutant cell lines treated for 72 h with BYL719 1 µM, MK2206 1 µM, Rapamycin 10 nM, RMC-6272 1 nM, RapaLink-1 10 nM, Adagrasib 100 nM, RM-018 100 nM, or combination treatments as indicated. Each point represents the mean of n = 8 experimental replicates, and the boxes represent the mean of the cell lines. e Cell viability as percentage change from control for KRAS^G12C mutant cell lines treated with either 100 nM RM-018, 1 nM RMC-6272 or the combination for 72 h. Data are means ± SD for n = 8 experimental replicates. P values are shown and were calculated by one-way ANOVA with post-hoc Tukey’s test. The status of genetic co-alterations is shown.