A Perspective on the Development of TGF-ß Inhibitors for Cancer Treatment.
Biomolecules
; 9(11)2019 11 17.
Article
em En
| MEDLINE
| ID: mdl-31744193
ABSTRACT
Transforming growth factor (TGF)-ß is a secreted multifunctional cytokine that signals via plasma membrane TGF-ß type I and type II receptors and intercellular SMAD transcriptional effectors. Aberrant inter- and intracellular TGF-ß signaling can contribute to cancer progression. In normal cells and early stages of cancer, TGF-ß can stimulate epithelial growth arrest and elicit a tumor suppressor function. However, in late stages of cancer, when the cytostatic effects of TGF-ß in cancer cells are blocked, TGF-ß 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-ß signaling in cancer and summarize the clinical status of TGF-ß signaling inhibitors that interfere with TGFïß bioavailability, TGF-ßï¯receptor interaction, or TGF-ß receptor kinase function. Moreover, we will discuss targeting of TGF-ß signaling modulators and downstream effectors as well as alternative approaches by using promising technologies that may lead to entirely new classes of drugs.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Fator de Crescimento Transformador beta
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Proteínas de Neoplasias
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Neoplasias
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Antineoplásicos
Limite:
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article