The death receptor ligand TRAIL has shown remarkable promise as an anticancer agent. However, TRAIL signaling also activates NF-κB, 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-κB-mediated transcription of Mcl-1. These findings suggest that combining TRAIL with agents that disrupt NF-κB regulation or binding or those that directly destabilize or disable Mcl-1 will have therapeutic benefit. © 2007 Elsevier Inc. All rights reserved.
Hall, M. A., & Cleveland, J. L. (2007, July 10). Clearing the TRAIL for Cancer Therapy. Cancer Cell. https://doi.org/10.1016/j.ccr.2007.06.011