Abstract
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) induces apoptosis selectively via its interaction with the death receptors TRAILR1/DR4 and TRAILR2/DR5 in a wide range of cancers, while sparing normal cells. Despite its tremendous potential for cancer therapeutics, the translation of TRAIL into the clinic has been confounded by TRAIL-resistant cancer populations. We discuss different molecular mechanisms underlying TRAIL-mediated apoptosis and resistance to TRAIL. We also discuss the successes and failures of recent preclinical and clinical studies of TRAIL-induced apoptosis, and current attempts to overcome TRAIL resistance, and we provide a perspective for improving the prospects of future clinical implementation.
Keywords:
TRAIL; apoptosis; cancer; therapeutic resistance.
Copyright © 2020 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Antineoplastic Combined Chemotherapy Protocols / pharmacology*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Apoptosis / drug effects*
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Apoptosis / genetics
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Apoptosis / radiation effects
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Cell Line, Tumor
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Chemoradiotherapy / methods
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Clinical Trials as Topic
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DNA Damage / drug effects
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DNA Damage / radiation effects
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Drug Resistance, Neoplasm / drug effects
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Drug Resistance, Neoplasm / genetics
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Drug Resistance, Neoplasm / radiation effects
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Drug Screening Assays, Antitumor
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Epigenesis, Genetic / drug effects
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Gene Expression Regulation, Neoplastic / drug effects
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Half-Life
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Humans
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Immunotherapy / methods
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Neoplasms / genetics
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Neoplasms / pathology
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Neoplasms / therapy*
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Receptors, TNF-Related Apoptosis-Inducing Ligand / metabolism
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Signal Transduction / drug effects
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Signal Transduction / genetics
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TNF-Related Apoptosis-Inducing Ligand / pharmacology*
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TNF-Related Apoptosis-Inducing Ligand / therapeutic use
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Treatment Outcome
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Tumor Microenvironment / drug effects
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Tumor Microenvironment / genetics
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Tumor Microenvironment / radiation effects
Substances
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10A protein, human
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TNFRSF10B protein, human
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TNFSF10 protein, human