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Targeting TGF-? Signaling for Therapeutic Gain.


ABSTRACT: Transforming growth factor ?s (TGF-?s) are closely related ligands that have pleiotropic activity on most cell types of the body. They act through common heterotetrameric TGF-? type II and type I transmembrane dual specificity kinase receptor complexes, and the outcome of signaling is context-dependent. In normal tissue, they serve a role in maintaining homeostasis. In many diseased states, particularly fibrosis and cancer, TGF-? ligands are overexpressed and the outcome of signaling is diverted toward disease progression. There has therefore been a concerted effort to develop drugs that block TGF-? signaling for therapeutic benefit. This review will cover the basics of TGF-? signaling and its biological activities relevant to oncology, present a summary of pharmacological TGF-? blockade strategies, and give an update on preclinical and clinical trials for TGF-? blockade in a variety of solid tumor types.

SUBMITTER: Akhurst RJ 

PROVIDER: S-EPMC5630004 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Targeting TGF-β Signaling for Therapeutic Gain.

Akhurst Rosemary J RJ  

Cold Spring Harbor perspectives in biology 20171003 10


Transforming growth factor βs (TGF-βs) are closely related ligands that have pleiotropic activity on most cell types of the body. They act through common heterotetrameric TGF-β type II and type I transmembrane dual specificity kinase receptor complexes, and the outcome of signaling is context-dependent. In normal tissue, they serve a role in maintaining homeostasis. In many diseased states, particularly fibrosis and cancer, TGF-β ligands are overexpressed and the outcome of signaling is diverted  ...[more]

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