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Pharmacological interventions in the Wnt pathway: Inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors


Zimmerli, Dario; Hausmann, George; Cantù, Claudio; Basler, Konrad (2017). Pharmacological interventions in the Wnt pathway: Inhibition of Wnt secretion versus disrupting the protein-protein interfaces of nuclear factors. British Journal of Pharmacology, 174(24):4600-4610.

Abstract

Mutations in components of the Wnt pathways are a frequent cause of many human diseases, particularly cancer. Despite the fact that a causative link between aberrant Wnt signaling and many types of human cancers was established more than a decade ago, no Wnt signaling inhibitors have made it into the clinic so far. One reason for this is that no pathway-specific kinase is known. Additionally targeting the protein-protein interactions needed to transduce the signal has not met with success so far. Complicating the search for and use of inhibitors is the complexity of the cascades triggered by the Wnts and their paramount biological importance. Wnt/β-catenin signaling is involved in virtually all aspects of embryonic development and in the control of the homeostasis of adult tissues. Encouragingly however, in recent years first successes with Wnt-pathway inhibitors have been reported in mouse models of disease. In this review we summarize possible roads to follow during the quest to pharmacologically modulate the Wnt signaling pathway in cancer.

Abstract

Mutations in components of the Wnt pathways are a frequent cause of many human diseases, particularly cancer. Despite the fact that a causative link between aberrant Wnt signaling and many types of human cancers was established more than a decade ago, no Wnt signaling inhibitors have made it into the clinic so far. One reason for this is that no pathway-specific kinase is known. Additionally targeting the protein-protein interactions needed to transduce the signal has not met with success so far. Complicating the search for and use of inhibitors is the complexity of the cascades triggered by the Wnts and their paramount biological importance. Wnt/β-catenin signaling is involved in virtually all aspects of embryonic development and in the control of the homeostasis of adult tissues. Encouragingly however, in recent years first successes with Wnt-pathway inhibitors have been reported in mouse models of disease. In this review we summarize possible roads to follow during the quest to pharmacologically modulate the Wnt signaling pathway in cancer.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Institute of Molecular Life Sciences
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:18 May 2017
Deposited On:20 Jun 2017 14:54
Last Modified:01 Jun 2018 00:45
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:0007-1188
OA Status:Green
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1111/bph.13864
PubMed ID:28521071

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