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Cancer Cell. 2007 Jul;12(1):4-6.

Clearing the TRAIL for Cancer Therapy.

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Department of Cancer Biology, The Scripps Research Institute-Florida, Jupiter, FL 334548, USA.


The death receptor ligand TRAIL has shown remarkable promise as an anticancer agent. However, TRAIL signaling also activates NF-kappaB, which induces the antiapoptotic regulators Mcl-1 and cIAP2, thus compromising its efficacy. In this issue of Cancer Cell, El-Deiry and colleagues explore pathways that disrupt TRAIL-induced survival signaling and show that the Myc oncoprotein and the Raf kinase inhibitor Sorafenib sensitize otherwise TRAIL-resistant colon cancer cells by effectively reducing NF-kappaB-mediated transcription of Mcl-1. These findings suggest that combining TRAIL with agents that disrupt NF-kappaB regulation or binding or those that directly destabilize or disable Mcl-1 will have therapeutic benefit.

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