title: Clearing the TRAIL for Cancer Therapy.
abstract: 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.
authors.affiliation: Department of Cancer Biology, The Scripps Research Institute-Florida, Jupiter, FL 334548, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hall
authors.forename: John L
authors.initials: JL
authors.lastname: Cleveland
mesh_terms: D017209:Apoptosis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human