Fig. 2.

Identification of lorlatinib-resistant G1202R + G1269A double mutation in a mouse xenograft model using patient-derived ALK-G1202R positive cells.

(a) Graphic depicting the scheme to establish the lorlatinib-resistant tumor is presented. (b) The sequence of JFCR-041-2 LorR cells. (c) Suppression of phospho-ALK and its downstream signaling in JFCR-041-2 or JFCR-041-2 LorR cells by ALK-TKI treatment. Cells were exposed to 300 nM of each ALK-TKI for 3 h. Cell lysates were immunoblotted to detect the indicated proteins. (d and e) Suppression of phospho-ALK and its downstream signaling by lorlatinib (d) or brigatinib (e) in each Ba/F3 cells. Cells were exposed to increasing concentrations (10 nM, 100 nM, 300 nM, 600 nM and 1000 nM) of each inhibitor for 3 h. Cell lysates were immunoblotted to detect the indicated proteins.