Although it has been suggested that differential binding affinities of the pro-apoptotic proteins, such as BAK (binds Bcl-xL, Bcl-2, and Mcl-1) and BAX (only binds Bcl-xL and Mcl-1), could explain differences in activity between the drug combinations, knockout of both BAX and BAK in melanoma had a similar influence on all BH3-mimetic combinations (12). This evidence concerns the gene BCL2 and melanoma.