Clearing the TRAIL for Cancer Therapy

Cancer Cell. 2007 Jul;12(1):4-6. doi: 10.1016/j.ccr.2007.06.011.


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.

Publication types

  • Comment
  • Review

MeSH terms

  • Apoptosis
  • Humans
  • Neoplasms / metabolism
  • Neoplasms / therapy*
  • Signal Transduction
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*


  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human