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Cold Spring Harb Perspect Biol. 2017 Oct 3;9(10). pii: a022301. doi: 10.1101/cshperspect.a022301.

Targeting TGF-β Signaling for Therapeutic Gain.

Author information

1
Department of Anatomy and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California 94158-9001.

Abstract

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 toward disease progression. There has therefore been a concerted effort to develop drugs that block TGF-β signaling for therapeutic benefit. This review will cover the basics of TGF-β signaling and its biological activities relevant to oncology, present a summary of pharmacological TGF-β blockade strategies, and give an update on preclinical and clinical trials for TGF-β blockade in a variety of solid tumor types.

PMID:
28246179
DOI:
10.1101/cshperspect.a022301
[Indexed for MEDLINE]

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