MRTX1133 and afatinib combination remains effective in cells that have acquired MRTX1133 resistance. A and B, Cell viability of parental and MRTXR SUIT2 lines after treatment with MRTX1133 (A) or afatinib (B). C, Evaluation of the synergistic effect of MRTX1133 with afatinib using the BLISS and HSA synergy models in MRTXR SUIT2. D and E, Immunoblot analysis for the upstream and downstream signaling of KRAS after single-agent (D) or combination therapy with MRTX1133 and afatinib (E). F, qRT-PCR analysis KRAS expression in parental and MRTXR SUIT2 cells. G, Immunoblot analysis for RASG12D in parental or MRTXR SUIT2. H, Immunoblot analysis of RASG12D and pan-RAS in parental SUIT2, untreated MRTXR SUIT2, and MRTX1133-treated MRTXR SUIT2 after RAS-GTP pulldown. I, Quantification of H. Values are quantifications from two different Western blots normalized to 0.6% GAPDH input. Data, mean values ± SD. Immunoblots are representative of at least three independent experiments.