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This Podcast features a conversation with authors of a Research Article published in the 10 January 2012 issue of Science Signaling. Travis Biechele, Andy Chien, and Randy Moon discuss their finding that some melanoma cell lines exhibited increased cell death (apoptosis) when signaling through the kinase BRAF was inhibited simultaneously with activation of the Wnt/β-catenin pathway. Melanoma is an aggressive form of skin cancer that is sometimes associated with an activated mutant version of BRAF (BRAFV600E). Some melanoma patients with this mutation fail to exhibit long-term responsiveness to inhibition of BRAF, so additional therapies are needed to overcome this resistance to apoptosis. The findings reported in this study suggest that inhibiting BRAF concomitantly with stimulating Wnt/β-catenin signaling may be an effective strategy for restoring susceptibility to apoptosis in apoptosis-resistant melanomas.