Resistance Studies in Lung Cancer

TThe purpose of the study was to compare gene expression profiles from a cohort of crizotinib-resistant ALK-rearranged lung tumors and a cohort of treatment-naive ALK-rearranged lung tumors, and to study resistance mechanism and tumor heterogeneity from a cohort of erlotinib-resistant EGFR-mutant lung adenocarcinoma patients. Expression profiles were generated by RNA-seq from the ALK-rearranged tumors. In parallel, gene expression profiles were obtained from ALK-rearranged lung cancer cell lines in the presence or absence of the ALK inhibitor TAE684. Gene expression profiles were also obtained from ALK-rearranged cells ectopically expressing genes associated with ALK inhibitor resistance that were identified from a functional genetic study. Whole-exome sequencing was performed on the erlotinib-resistant tumors. Previously known and novel resistance mechanisms were identified from the somatic mutations and copy number changes. Validation of the resistant... (for more see dbGaP study page.)