Breast cancer proteome takes more than two to tango on TRAIL: beat them at their own game.

Breast carcinogenesis is a multidimensional disease that has resisted drug-related solutions to date because of heterogeneity, disorganized spatiotemporal behavior of signal transduction cascades, cell cycle checkpoints, cell transition, plasticity, and impaired pro-apoptotic response. These synchronized oncogenic events, including protein-protein interaction, transcriptional-regulatory, and signaling networks, trigger genomic and transcriptional disturbances in TRAIL-mediated signaling network neighborhoods. Therefore, tumor cells often acquire the ability to escape death by suppressing cell death pathways that normally function to eliminate damaged and harmful cells. This review describes the TRAIL-mediated cell death signaling pathways, the interactions between these pathways, and the ways in which these pathways are deregulated in breast cancer.