Furthermore, it remains to be verified whether the combination of MEK or PI3K/mTOR inhibitors with death receptor agonists (such as TRAIL itself or DR5-specific mAbs) may also exert significant pro-apoptotic effects in vivo on melanoma xenografts and whether this is associated with inhibition of relevant pro-tumoral processes in the tumor microenvironment. This evidence concerns the gene TNFSF10 and melanoma.