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Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy

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Science Signaling  07 Apr 2015:
Vol. 8, Issue 371, pp. rs3
DOI: 10.1126/scisignal.2005700

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Networking death signals

Selective killing of cancer cells without the induction of resistance is the holy grail of cancer therapy. TRAIL is an endogenous secreted protein that promotes cell death, and cancer cells are particularly sensitive to this molecule. Unfortunately, some cancer cells evade TRAIL-induced death and develop resistance by rewiring their signaling networks. So et al. took a proteomic approach aimed at kinases, which are key regulators of cell survival and death, and mapped a protein interaction network encompassing kinases that they identified as affecting TRAIL-induced cell death. Modeling information flow through the network revealed potential targets that could be exploited to develop combination therapies with TRAIL to kill cancer cells and prevent resistance.