 This phase II study in 20 patients with BRAFV600E mutant, unresectable stage IIIIV melanoma is designed to explore the mechanisms by which tumors acquire resistance to the combination of a BRAF inhibitor dabrafenib and MEK inhibitor trametinib. Tissue will be collected at baseline and at progression. Markers of resistance will be explored by performing near kinome-wide profiling on tumor samples, and in patients who co-enroll in institutional protocol LCCC1108, by sequencing tumors using NextGen DNA sequencing technology. Overall response rate and duration to this combination will also be assessed. 