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. Author manuscript; available in PMC: 2019 Jul 1.
Published in final edited form as: Mol Cancer Ther. 2018 Apr 13;17(7):1526–1539. doi: 10.1158/1535-7163.MCT-17-0464

Figure 6. BGJ398 in combination with Trametinib hinders the establishment of drug-resistance.

Figure 6

A) Quantification of colony formation for NCI-H520, DMS114 and AN3 CA cell lines treated for 4 weeks with BGJ398 (BGJ), trametinib (Tram) or combination (BGJ + Tram), shown as a percentage of the control. Mean (3 biological replicates) +/− standard deviation (SD) shown (* p-value < 0.05, ** < 0.005, *** < 0.0005, two-sided t-test).

B) Tumor volume index normalized to pre-treatment volume for NCI-H2077 xenografts treated with the indicated drugs for 8 weeks (n=5 mice in each treatment group, equivalent to 10 tumors in each group). Mean +/− SEM shown.

C) Progression-free survival for NCI-H2077 xenografts treated as in (B). Progression-free survival over time is shown as a percentage for each treatment group. Log-rank (Mantel-Cox) test analysis (p-value<0.0001).

D) Immunoblot analysis for FRS2, AKT and ERK activity for NCI-H2077 cells treated for 48 hours with DMSO, BGJ398, or additional kinase inhibitors as indicated, or combination treatment as indicated. (Tram, Trametinib; LDC, LDC1267; LOXO, LOXO-101; Imat, Imatinib; MGCD, MGCG-265).