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Media type:
E-Article
Title:
A Perspective on the Development of TGF-β Inhibitors for Cancer Treatment
Contributor:
Huynh, Linh;
Hipolito, Christopher;
ten Dijke, Peter
imprint:
MDPI AG, 2019
Published in:Biomolecules
Language:
English
DOI:
10.3390/biom9110743
ISSN:
2218-273X
Origination:
Footnote:
Description:
<jats:p>Transforming growth factor (TGF)-β is a secreted multifunctional cytokine that signals via plasma membrane TGF-β type I and type II receptors and intercellular SMAD transcriptional effectors. Aberrant inter- and intracellular TGF-β signaling can contribute to cancer progression. In normal cells and early stages of cancer, TGF-β can stimulate epithelial growth arrest and elicit a tumor suppressor function. However, in late stages of cancer, when the cytostatic effects of TGF-β in cancer cells are blocked, TGF-β signaling can act as tumor promoter by its ability to stimulate epithelial-to-mesenchymal transition of cancer cells, by stimulating angiogenesis, and by promoting evasion of immune responses. In this review, we will discuss the rationale and challenges of targeting TGF-β signaling in cancer and summarize the clinical status of TGF-β signaling inhibitors that interfere with TGF−β bioavailability, TGF-β/receptor interaction, or TGF-β receptor kinase function. Moreover, we will discuss targeting of TGF-β signaling modulators and downstream effectors as well as alternative approaches by using promising technologies that may lead to entirely new classes of drugs.</jats:p>