The increased sensitivity of the A375 melanoma model cell lines to BRAF inhibitor in 3D relative to 2D tissue culture, and the increased sensitivity of the MEK1 Q56P isogenic A375 melanoma model to both MEK inhibitor and combination MEK/BRAF inhibitor when grown in 3D tissue culture highlight the utility of the 3D tissue culture format for high-throughput drug screening. Here, MAP2K1 is linked to melanoma.