Universität zu Köln

Kretz, Anna-Laura, Trauzold, Anna, Hillenbrand, Andreas, Knippschild, Uwe, Henne-Bruns, Doris, von Karstedt, Silvia and Lemke, Johannes ORCID: 0000-0003-2142-6097 (2019). TRAILblazing Strategies for Cancer Treatment. Cancers, 11 (4). BASEL: MDPI. ISSN 2072-6694

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kretz, Anna-Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Trauzold, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Hillenbrand, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Knippschild, Uwe UNSPECIFIED UNSPECIFIED UNSPECIFIED Henne-Bruns, Doris UNSPECIFIED UNSPECIFIED UNSPECIFIED von Karstedt, Silvia UNSPECIFIED UNSPECIFIED UNSPECIFIED Lemke, Johannes UNSPECIFIED orcid.org/0000-0003-2142-6097 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-151461
DOI:	10.3390/cancers11040456
Journal or Publication Title:	Cancers
Volume:	11
Number:	4
Date:	2019
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2072-6694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TUMOR-NECROSIS-FACTOR; TRAIL-INDUCED APOPTOSIS; NF-KAPPA-B; DEATH RECEPTOR 5; FLICE-INHIBITORY PROTEIN; BCL-X-L; CHRONIC LYMPHOCYTIC-LEUKEMIA; FOLFOX6 PLUS BEVACIZUMAB; FADD-DEPENDENT APOPTOSIS; CELL LUNG-CANCER Multiple languages Oncology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/15146