Whole exome sequencing of ALK and ROS1 cells resistant to targeted therapies

Despite the initial benefit of the tyrosine kinase inhibitors (TKIs) targeting ALK and ROS1 fusion kinases in non-small cell lung cancer, resistance to those targeted therapies is almost inevitable. To determine the acquired resistance mechanism, we generated several ALK and ROS1 resistant cells by chronically treating them with ALK and ROS1 TKIs. In addition, because we have demonstrated EGFR could mediate the early adaptive resistance to fusion kinase inhibition, we have generated cell lines resistant to the combination of ALK and EGFR inhibitors. Whole exome sequencing was performed to determine whether acquired resistance mutations developed in those resistant cells compared to their parental counterparts.