a, Western blot from the two colorectal cancer cell lines LMNA-NTRK1, NTRK1 G595R and LMNA-NTRK1, NTRK1 G595R, KRAS G12D, treated as indicated. LOXO-195 (50nM), MEK-162 (50nM) or the combination of both drugs (195 + 162) were administered at the indicated time and protein lysates were probed with the indicated antibodies. While LOXO-195 was sufficient to inhibit both phospo-TRK and phospho-ERK in the KRAS wild type cell line, the combination of LOXO-195 and MEK-162 was required for this dual inhibition in the KRAS G12D mutated cell line. Three biological replicates were performed. b, Proliferation assays on the same cell lines (labeled NTRK1 G595R and KRAS G12D, respectively) treated for 72 hours with LOXO-195 (125nM), MEK-162 (25nM) or their combination. Data are presented as mean ± SD of four biological replicates. Two-tailed unpaired t-test was used to evaluate significant differences in % of viable cells. P values <0.05 were considered statistically significant.