Cargando…

TRAILblazing Strategies for Cancer Treatment

In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound d...

Descripción completa

Detalles Bibliográficos
Autores principales: Kretz, Anna-Laura, Trauzold, Anna, Hillenbrand, Andreas, Knippschild, Uwe, Henne-Bruns, Doris, von Karstedt, Silvia, Lemke, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521007/
https://www.ncbi.nlm.nih.gov/pubmed/30935038
http://dx.doi.org/10.3390/cancers11040456
_version_ 1783418857221783552
author Kretz, Anna-Laura
Trauzold, Anna
Hillenbrand, Andreas
Knippschild, Uwe
Henne-Bruns, Doris
von Karstedt, Silvia
Lemke, Johannes
author_facet Kretz, Anna-Laura
Trauzold, Anna
Hillenbrand, Andreas
Knippschild, Uwe
Henne-Bruns, Doris
von Karstedt, Silvia
Lemke, Johannes
author_sort Kretz, Anna-Laura
collection PubMed
description In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities. Thus, several so-called TRAIL receptor agonists (TRAs) were developed. Unfortunately, clinical testing of these TRAs did not reveal any significant anticancer activity, presumably due to inherent or acquired TRAIL resistance of most primary tumour cells. Since the potential power of TRAIL-based therapies still lies in TRAIL’s explicit cancer cell-selectivity, a desirable approach going forward for TRAIL-based cancer therapy is the identification of substances that sensitise tumour cells for TRAIL-induced apoptosis while sparing normal cells. Numerous of such TRAIL-sensitising strategies have been identified within the last decades. However, many of these approaches have not been verified in animal models, and therefore potential toxicity of these approaches has not been taken into consideration. Here, we critically summarise and discuss the status quo of TRAIL signalling in cancer cells and strategies to force tumour cells into undergoing apoptosis triggered by TRAIL as a cancer therapeutic approach. Moreover, we provide an overview and outlook on innovative and promising future TRAIL-based therapeutic strategies.
format Online
Article
Text
id pubmed-6521007
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-65210072019-05-31 TRAILblazing Strategies for Cancer Treatment Kretz, Anna-Laura Trauzold, Anna Hillenbrand, Andreas Knippschild, Uwe Henne-Bruns, Doris von Karstedt, Silvia Lemke, Johannes Cancers (Basel) Review In the late 1990s, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF-family, started receiving much attention for its potential in cancer therapy, due to its capacity to induce apoptosis selectively in tumour cells in vivo. TRAIL binds to its membrane-bound death receptors TRAIL-R1 (DR4) and TRAIL-R2 (DR5) inducing the formation of a death-inducing signalling complex (DISC) thereby activating the apoptotic cascade. The ability of TRAIL to also induce apoptosis independently of p53 makes TRAIL a promising anticancer agent, especially in p53-mutated tumour entities. Thus, several so-called TRAIL receptor agonists (TRAs) were developed. Unfortunately, clinical testing of these TRAs did not reveal any significant anticancer activity, presumably due to inherent or acquired TRAIL resistance of most primary tumour cells. Since the potential power of TRAIL-based therapies still lies in TRAIL’s explicit cancer cell-selectivity, a desirable approach going forward for TRAIL-based cancer therapy is the identification of substances that sensitise tumour cells for TRAIL-induced apoptosis while sparing normal cells. Numerous of such TRAIL-sensitising strategies have been identified within the last decades. However, many of these approaches have not been verified in animal models, and therefore potential toxicity of these approaches has not been taken into consideration. Here, we critically summarise and discuss the status quo of TRAIL signalling in cancer cells and strategies to force tumour cells into undergoing apoptosis triggered by TRAIL as a cancer therapeutic approach. Moreover, we provide an overview and outlook on innovative and promising future TRAIL-based therapeutic strategies. MDPI 2019-03-30 /pmc/articles/PMC6521007/ /pubmed/30935038 http://dx.doi.org/10.3390/cancers11040456 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Kretz, Anna-Laura
Trauzold, Anna
Hillenbrand, Andreas
Knippschild, Uwe
Henne-Bruns, Doris
von Karstedt, Silvia
Lemke, Johannes
TRAILblazing Strategies for Cancer Treatment
title TRAILblazing Strategies for Cancer Treatment
title_full TRAILblazing Strategies for Cancer Treatment
title_fullStr TRAILblazing Strategies for Cancer Treatment
title_full_unstemmed TRAILblazing Strategies for Cancer Treatment
title_short TRAILblazing Strategies for Cancer Treatment
title_sort trailblazing strategies for cancer treatment
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521007/
https://www.ncbi.nlm.nih.gov/pubmed/30935038
http://dx.doi.org/10.3390/cancers11040456
work_keys_str_mv AT kretzannalaura trailblazingstrategiesforcancertreatment
AT trauzoldanna trailblazingstrategiesforcancertreatment
AT hillenbrandandreas trailblazingstrategiesforcancertreatment
AT knippschilduwe trailblazingstrategiesforcancertreatment
AT hennebrunsdoris trailblazingstrategiesforcancertreatment
AT vonkarstedtsilvia trailblazingstrategiesforcancertreatment
AT lemkejohannes trailblazingstrategiesforcancertreatment