The current study has shown that pre-treatment of Ras-mutant cancer cell lines with PLX4032 sensitizes them to TRAIL-induced apoptosis; this effect is clearly due to c-Raf/MEK/ERK-dependent upregulation of DR5 expression because inhibition of MEK (e.g., with AZD6244) or c-Raf (e.g., with c-Raf siRNAs) abrogated the ability of PLX4032 not only to increase DR5 expression, but also to sensitize Ras-mutant cancer cells to TRAIL-induced apoptosis. This evidence concerns the gene TNFRSF10B and cancer.