A Cell viability of KRASG12C LUAD cells (H1792, HCC44, H23, H358 and CP435) treated with Sotorasib (Soto; 20–500 nM), Midostaurin (Mido; 0.3–1.25 μM) or both (72-h treatment; data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment). B Cell viability of KRASG12C cells (H1792, HCC44 and H358) in 3D (72-h treatment). Soto: 62.5 nM; Mido: 0.3 μM (data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment). C Representative images of H1792, HCC44 and H358 3D cultures exposed to treatments. Scale bar: 200 μm. D Effects of Soto and Mido combination on cell viability of mut KRAS patient-derived xenograft organoids (PDXOs: TP60, TP69, TP80, TP181, TP126) in 3D (72-h treatment). Soto: 62 nM; Mido: 0.3 μM (data: mean +/− SD; test: one-way ANOVA, Dunnet’s adjustment). E Percent cell viability of KRASG12C cells (H1792, HCC44, H23, H358 and CP435) treated with Soto (S), Mido (M), Tram (T), Afatinib (Afati, A) or combinations for 72 h (data: mean +/− SD; test: oneway ANOVA, Bonferroni’s adjustment). F Percent cell viability of KRASG12C cells (H1792, HCC44, and H358) grown in 3D, after 72 h treatment with Soto (S), Mido (M), Tram (T), Afati (A) or indicated combinations (data: mean +/− SD; test: one-way ANOVA, Bonferroni’s adjustment). G Representative crystal violet staining images of 10-day treatment (control: Ctrl; Soto: 12,5-62,5 nM; Mido: 50–100 nM). H Long-term effect of Soto and Mido combination on cell viability of KRASG12C cells (H1792, HCC44, H23 and H358). 10-day treatment (data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment). I Cell viability percentage of Soto-resistant (SR) H23 and H358 cells treated with indicated concentrations of Soto and Mido, individually or in combination (average of 3 experiments). J Western blot analysis of indicated proteins in H1792 and HCC44 KRASG12C cells (48-h treatments; loading control: ACTIN; exposure time: low and high). K Effects of Soto and Barasertib (Bara) combination on cell viability of mut KRAS (H1792, HCC44, H23, H358) cells (72-h treatment; Soto: 0.02 − 5 µM; Bara: 5 μM; (data: mean +/− SD; test: one-way ANOVA, Tukey’s adjustment).