Mcl-1 : A Gateway to TRAIL Sensitization

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...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2008-04, Vol.68 (7), p.2062-2064
Main Authors: KIM, Seok-Hyun, STACEY RICCI, M, EL-DEIRY, Wafik S
Format: Article
Language:English
Subjects:
Antineoplastic agents
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Benzenesulfonates - administration & dosage
Benzenesulfonates - pharmacology
Biological and medical sciences
Down-Regulation
Drug Resistance, Neoplasm
Drug Synergism
Humans
Leukemia - drug therapy
Leukemia - genetics
Leukemia - metabolism
Medical sciences
Myeloid Cell Leukemia Sequence 1 Protein
Neoplasm Proteins - antagonists & inhibitors
Neoplasm Proteins - biosynthesis
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Niacinamide - analogs & derivatives
Pharmacology. Drug treatments
Phenylurea Compounds
Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-bcl-2 - genetics
Proto-Oncogene Proteins c-bcl-2 - metabolism
Pyridines - administration & dosage
Pyridines - pharmacology
TNF-Related Apoptosis-Inducing Ligand - administration & dosage
TNF-Related Apoptosis-Inducing Ligand - pharmacology
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-07-6278