Abstract
Since the discovery of tumor necrosis factor (TNF)-alpha, researchers have pursued many approaches to harness the potency of TNF-alpha and TNF superfamily members to treat human cancers. Several ligands of the TNF superfamily, including TNF-alpha, lymphotoxin, FAS ligand (FasL), and APO2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) have been tested in various stages of clinical research for their anti-tumor efficacy. Moreover, several antibodies to TNF receptor (TNFR) superfamily members are now being explored as cancer therapeutics. Due to the toxicity associated with delivering TNF-alpha systemically at clinically relevant doses, more targeted methods are now seen as a likely alternative to provide a localized therapeutically effective dose of TNF-alpha. In this review we revisit historical attempts to use TNF-alpha to treat human cancer, and put this into the context of more recent targeted strategies to circumvent TNF-alphas systemic toxicity. We will attempt to integrate the results of pre-clinical and clinical trials with a concise synopsis of the TNF-alpha signaling network, with the goal of reconciling our understanding of how the cell biology and tumor biology mechanistically relate.
Current Cancer Drug Targets
Title: Tumor Necrosis Factor: Renaissance as a Cancer Therapeutic?
Volume: 8 Issue: 2
Author(s): D. Daniel and N. S. Wilson
Affiliation:
Abstract: Since the discovery of tumor necrosis factor (TNF)-alpha, researchers have pursued many approaches to harness the potency of TNF-alpha and TNF superfamily members to treat human cancers. Several ligands of the TNF superfamily, including TNF-alpha, lymphotoxin, FAS ligand (FasL), and APO2 ligand/TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) have been tested in various stages of clinical research for their anti-tumor efficacy. Moreover, several antibodies to TNF receptor (TNFR) superfamily members are now being explored as cancer therapeutics. Due to the toxicity associated with delivering TNF-alpha systemically at clinically relevant doses, more targeted methods are now seen as a likely alternative to provide a localized therapeutically effective dose of TNF-alpha. In this review we revisit historical attempts to use TNF-alpha to treat human cancer, and put this into the context of more recent targeted strategies to circumvent TNF-alphas systemic toxicity. We will attempt to integrate the results of pre-clinical and clinical trials with a concise synopsis of the TNF-alpha signaling network, with the goal of reconciling our understanding of how the cell biology and tumor biology mechanistically relate.
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Cite this article as:
Daniel D. and Wilson S. N., Tumor Necrosis Factor: Renaissance as a Cancer Therapeutic?, Current Cancer Drug Targets 2008; 8 (2) . https://dx.doi.org/10.2174/156800908783769346
DOI https://dx.doi.org/10.2174/156800908783769346 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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