Fig. 3

Mechanisms of resistance to ALK inhibitors. Resistance to ALK inhibitors may be mediated by acquired secondary mutations in the ALK kinase domain (F1174 L, F1174C, L1196 M, I1171T, G1202R, S1206Y, G1269S, and G1269A) or ALK gene amplification indicating the persistance of ALK dependency. Resistance can also be mediated by activation of alternative survival pathways such as the EGFR or the insulin-like growth factor pathways