Effect of combination treatment with BRAF and MEK inhibitors (BRAFi/MEKi) in BRAFV600E mutant cell lines using RNAseq

We defined the molecular alterations associated with acquired resistance using combined treatment with BRAFi/MEKi in melanoma cell lines. After the successful establishment of six resistant cell lines, we determined the invasion properties and gene/protein expression differences between sensitive and resistant cells. We observed that the in-vasive potential of three of six resistant cell lines increased significantly compared to sensitive cell lines. We also observed that resistant cells were not drug addicted and did not exhibit significantly increased lethality following the “drug holiday”. RNA sequencing (RNA-Seq) analysis showed that the differentially expressed genes were associated with epithelial-mesenchymal tran-sition (EMT), the reactive oxygen species (ROS) pathway, and KRAS signalling Examination of molecular alterations using RNAseq to study the effect of combination treatment with encorafenib and binimetinib.