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. Author manuscript; available in PMC: 2022 Aug 1.
Published in final edited form as: Mol Cancer Ther. 2021 Nov 17;21(2):322–335. doi: 10.1158/1535-7163.MCT-21-0344

Figure 2.

Figure 2

Combinations of type I and II MET TKIs can prevent resistance emergence. A, TPR MET Ba/F 3 cells were mutagenized with ENU and treated with single agent MET TKIs at 0.3 μM or their combinations in a 96 well format until resistant clones emerged. Wells with resistant outgrowth were counted and totals plotted as percentage of total seeded wells. B, The latency to resistance emergence is expressed as percentages of resistance clones emerging as a function of time in weeks. C, DNA from randomly selected resistant clones per TKI concentration was harvested and sequenced to detect secondary mutations in the MET TKD. The distribution of secondary mutants is expressed as percentages of the total number of resistant clones with an identified secondary mutation per drug treatment (n). D, Western blot of TPR-MET inhibition in NIH3T3 in response to 4h treatment with each TKI at 0, 0.1 and 1uM. HSP90 is used as a loading control. E, Vann diagram illustrating the cross-resistance of each tested MET TKI.