Resistance studies in Lung Cancer

The 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. Expression profiles were generated by RNA-seq. 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.]]> The presence of the EML4-ALK fusion protein was confirmed by RT-PCR for all patient-derived tumors before sequencing. Tumor specimens included in the treatment-naive cohort were obtained before treatment was initiated. Tumor specimens included in the crizotinib-resistant cohort were obtained after the development of resistance to crizotinib following an initial response to crizotinib. ]]>