The potential of TRAIL for cancer chemotherapy

Innate and acquired resistance to chemotherapy and radiation therapy has been a major obstacle for clinical oncology. One potential adjunct to such conventional treatments is direct induction of cell death by activation of death receptor-mediated apoptosis. TRAIL (tumor necrosis factor (TNF)-related...

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Bibliographic Details
Published in:Apoptosis (London) 2001-06, Vol.6 (3), p.191
Main Authors: Nagane, M, Huang, H J, Cavenee, W K
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Apoptosis
Apoptosis Regulatory Proteins
Cancer
Cancer therapies
Cells
Chemotherapy
Cytotoxicity
Humans
Ligands
Membrane Glycoproteins - therapeutic use
Mice
Models, Biological
Mortality
Neoplasm Transplantation
Neoplasms - drug therapy
Neoplasms - metabolism
Radiation therapy
Receptors, TNF-Related Apoptosis-Inducing Ligand
Receptors, Tumor Necrosis Factor - metabolism
Rodents
TNF-Related Apoptosis-Inducing Ligand
Tumor Necrosis Factor-alpha - therapeutic use
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Summary:Innate and acquired resistance to chemotherapy and radiation therapy has been a major obstacle for clinical oncology. One potential adjunct to such conventional treatments is direct induction of cell death by activation of death receptor-mediated apoptosis. TRAIL (tumor necrosis factor (TNF)-related apoptosis inducing ligand), a recently identified member of the growing TNF superfamily, binds to its cognate "death" receptors DR4 and DR5 as well as "decoy" receptors DcR1 and DcR2. Upon binding, rapid apoptosis is enacted in a variety of human cancer cell lines independent of p53 status, but not in normal cell lines. TRAIL treatment results in significant growth suppression of TRAIL-sensitive human cancer xenografts in mice. Furthermore, combination treatment of TRAIL with genotoxic chemotherapeutic agents synergistically suppresses growth of tumor xenografts which are otherwise resistant to treatment with TRAIL or chemotherapy alone. Unlike the other death ligands TNF-alpha or FasL, systemic administration of soluble human TRAIL does not cause toxicity in mice and non-human primates. While further studies are needed to evaluate the possible cytotoxicity of TRAIL especially for human hepatocytes, indications are increasing that TRAIL may be a novel therapeutic agent for human cancer.
ISSN:1360-8185
1573-675X
DOI:10.1023/A:1011336726649