Abstract
Triggering apoptosis, the cells intrinsic death program, is a promising approach for cancer therapy. TNF-related apoptosisinducing ligand (TRAIL), a member of the TNF superfamily of death inducing ligands, is of special interest for cancer therapy, since TRAIL has been shown to predominantly kill cancer cells, while sparing normal cells. However, since many cancers fail to undergo apoptosis in response to TRAIL treatment, TRAIL-based combination therapies have been developed for cancer-cell specific sensitization towards TRAIL. Chromatin remodelling plays an important role in gene regulation and aberrant architecture of the chromatin has been implicated in tumor formation and progression. In recent years, HDAC inhibitors (HDACI) that reverse aberrant epigenetic changes have emerged as a potential strategy to sensitize cancer cells for TRAIL-induced apoptosis. Synergistic tumor cell death has been reported in a variety of human cancers using different HDACI together with TRAIL. Here, recent advances in the understanding of the molecular events that underlie the synergistic interaction of HDACI and TRAIL are discussed as well as how this knowledge can be translated into the design of cancer-selective novel therapeutics.
Current Cancer Drug Targets
Title: Modulation of TRAIL-Induced Apoptosis by HDAC Inhibitors
Volume: 8 Issue: 2
Author(s): Simone Fulda
Affiliation:
Keywords: Apoptosis, TRAIL, HDACI, cancer
Abstract: Triggering apoptosis, the cells intrinsic death program, is a promising approach for cancer therapy. TNF-related apoptosisinducing ligand (TRAIL), a member of the TNF superfamily of death inducing ligands, is of special interest for cancer therapy, since TRAIL has been shown to predominantly kill cancer cells, while sparing normal cells. However, since many cancers fail to undergo apoptosis in response to TRAIL treatment, TRAIL-based combination therapies have been developed for cancer-cell specific sensitization towards TRAIL. Chromatin remodelling plays an important role in gene regulation and aberrant architecture of the chromatin has been implicated in tumor formation and progression. In recent years, HDAC inhibitors (HDACI) that reverse aberrant epigenetic changes have emerged as a potential strategy to sensitize cancer cells for TRAIL-induced apoptosis. Synergistic tumor cell death has been reported in a variety of human cancers using different HDACI together with TRAIL. Here, recent advances in the understanding of the molecular events that underlie the synergistic interaction of HDACI and TRAIL are discussed as well as how this knowledge can be translated into the design of cancer-selective novel therapeutics.
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Cite this article as:
Fulda Simone, Modulation of TRAIL-Induced Apoptosis by HDAC Inhibitors, Current Cancer Drug Targets 2008; 8 (2) . https://dx.doi.org/10.2174/156800908783769355
DOI https://dx.doi.org/10.2174/156800908783769355 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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