Targeting TGF-β Signaling in Cancer

The transforming growth factor (TGF)-beta 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-beta signaling make it a challenging target and imply the need for careful therapeutic dosing of TGF-beta drugs and patient selection. We review here the rationale for targeting TGF-beta signaling in cancer and summarize the clinical status of pharmacological inhibitors. We discuss the direct effects of TGF-beta signaling blockade on tumor and stromal cells, as well as biomarkers that can predict the efficacy of TGF-beta inhibitors in cancer patients.