Rapid transcriptional changes of ROS1 fusion positive cells in response to crizotinib treatments
Despite the initial benefit of tyrosine kinase inhibitors targeting ROS1 fusion kinase in non-small cell lung cancer, the complete responses are rare and resistance ultimately develops from residual tumor cells. Although several acquired resistance mechanisms after disease progression have been reported, the adaptative resistance mechanism that contributes to residual diseases before the onset of acquired resistance is less clear. Cellular adaption through the signaling rewiring under primary oncogene inhibition is considered a major mechanism contributing to residual disease. To explore the rapid signaling reprogramming under acute ROS1 inhibition, we treated a panel of ROS1 fusion-positive cells, mostly derived in our lab, with crizotinib for 24 hours and profiled transcriptional changes by RNA-seq. Understanding the molecular mechanism that supports residual disease could help us better target and eliminate drug-tolerant cells, thus improving the responses to ROS1 targeted therapies. Overall design: RNA was extracted from cells treated with DMSO or crizotinib for 24 hours in three biological replicates and subjected to RNA-seq.