A Perspective on the Development of TGF-? Inhibitors for Cancer Treatment.

ABSTRACT: Transforming growth factor (TGF)-? is a secreted multifunctional cytokine that signals via plasma membrane TGF-? type I and type II receptors and intercellular SMAD transcriptional effectors. Aberrant inter- and intracellular TGF-? signaling can contribute to cancer progression. In normal cells and early stages of cancer, TGF-? can stimulate epithelial growth arrest and elicit a tumor suppressor function. However, in late stages of cancer, when the cytostatic effects of TGF-? in cancer cells are blocked, TGF-? 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-? signaling in cancer and summarize the clinical status of TGF-? signaling inhibitors that interfere with TGF?? bioavailability, TGF-??receptor interaction, or TGF-? receptor kinase function. Moreover, we will discuss targeting of TGF-? signaling modulators and downstream effectors as well as alternative approaches by using promising technologies that may lead to entirely new classes of drugs.

SUBMITTER: Huynh LK 

PROVIDER: S-EPMC6921009 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature