Targeting TGF-β Signaling in Cancer

• Published in: Trends in cancer Vol. 3; no. 1; p. 56
• Main Authors: Colak, Selcuk, Ten Dijke, Peter
• Format: Journal Article
• Language: English
• Published: United States 01-01-2017
• Subjects: Animals; Biomarkers, Tumor - metabolism; Drug Resistance, Neoplasm; Humans; Neoplasms - drug therapy; Neoplasms - metabolism; Precision Medicine; Signal Transduction; Smad Proteins - metabolism; Transforming Growth Factor beta - antagonists & inhibitors; microenvironment; TGF-β; tumor-initiating cells; cancer; therapy resistance
• ISSN: 2405-8025
• DOI: 10.1016/j.trecan.2016.11.008

The transforming growth factor (TGF)-β signaling pathway is deregulated in many diseases, including cancer. In healthy cells and early-stage cancer cells, this pathway has tumor-suppressor functions, including cell-cycle arrest and apoptosis. However, its activation in late-stage cancer can promote tumorigenesis, including metastasis and chemoresistance. The dual function and pleiotropic nature of TGF-β signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-β drugs and patient selection. We review here the rationale for targeting TGF-β signaling in cancer and summarize the clinical status of pharmacological inhibitors. We discuss the direct effects of TGF-β signaling blockade on tumor and stromal cells, as well as biomarkers that can predict the efficacy of TGF-β inhibitors in cancer patients.