Fig. 2: Spontaneously formed ALK fusions induce resistance to osimertinib in PC-9 cells.
From: Mechanistic patterns and clinical implications of oncogenic tyrosine kinase fusions in human cancers
a Experimental timeline to select osimertinib-resistant clones in PC-9 cells. b Quantification of osimertinib-resistant clones in PC-9 cells treated as in (a). Data show means of ten biological replicates, with error bars representing ±s.e.m; significance was determined by an unpaired, two-tailed Student’s t-test. c Representative western blots of the signaling changes in osimertinib-resistant clones treated with EGFR inhibitor (osimertinib) and/or ALK inhibitor (lorlatinib). Red and blue arrows represent phosphorylated CDC42BPB-ALK and SQSTM1-ALK fusion proteins, respectively. Asterisk represents a non-specific band. Similar results were observed in n = 2 independent experiments. d Sensitivity to osimertinib (left), lorlatinib (middle), and combination of osimertinib plus lorlatinib (right) in osimertinib-resistant clones. Data show means of three biological replicates, with error bars representing ±s.e.m. e Circos plot showing the genome-wide distribution of ALK fusion partners identified in osimertinib-resistant PC-9 cells. Arcs represent functional rearrangements joining ALK (exon 20) to the indicated fusion partner. Source data are provided as a Source Data file.
