title: Mcl-1: a gateway to TRAIL sensitization.
abstract: The proapoptotic cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is being evaluated presently as a selective anticancer agent, but its limited effects against cancer cell lines has raised some concerns about its ultimate clinical utility. Here, we review recent findings that cancer cell sensitivity to TRAIL is greatly increased when the Bcl-2 family protein Mcl-1 is down-regulated by the Raf/vascular endothelial growth factor kinase inhibitor sorafenib, a Food and Drug Administration-approved cancer drug. Using the TRAIL-sorafenib combination as a tactic to more effectively kill cancer cells may provide an effective tool to attack a variety of human cancers that are largely presently untreatable.
authors.affiliation: Laboratory of Molecular Oncology and Cell Cycle Regulation, Department of Medicine, Institute for Translational Medicine and Therapeutics, Abramson Comprehensive Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: M Stacey
authors.initials: MS
authors.lastname: Ricci
authors.forename: Wafik S
authors.initials: WS
authors.lastname: El-Deiry
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001557:Benzenesulfonates / Q000008:administration & dosage / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D000077157:Sorafenib; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001557:Benzenesulfonates; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D011725:Pyridines; D053221:TNF-Related Apoptosis-Inducing Ligand; D009536:Niacinamide; D000077157:Sorafenib