Figure 3. Expression of ST7-MET Confers Resistance to ALK TKIs and Can Be Overcome by Dual ALK and MET Inhibition.

(A) and (B) Cell viability of H3122 cells with or without doxycycline-induced ST7-MET expression (DOX+ and DOX-, respectively) was measured after 3 days of monotherapy or combination therapy, as indicated. Viability was determined using CellTiter-Glo. Data are mean ± s.e.m. of three biological replicates. (C) Immunoblotting to assess phosphorylation of ALK, MET, and downstream targets in cells treated with lorlatinib and the MET TKIs shown. The arrowheads at 175 kDa and 145 kDa indicate the band for pro-MET and MET beta-chain respectively. Cells were treated with each drug at 300 nM for 6 hours. DOX: doxycycline.