Targeting TGF-β Signaling in Cancer

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• 作者：Selcuk Colak¹ ; ^{S.Colak@lumc.nl} ; Peter ten Dijke¹ ; ² ; ³ ; ^{P.ten_Dijke@lumc.nl}
• 关键词：TGF-β ; cancer ; therapy resistance ; microenvironment ; tumor-initiating cells
• 刊名：Trends in Cancer
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：3
• 期：1
• 页码：56-71
• 全文大小：4894 K
• 卷排序：3

文摘

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.