Molecular Pathways: Targeting the TGF-β Pathway for Cancer Therapy

TGF-beta is a ubiquitous cytokine that plays an active role in many cellular processes. Nearly every cell type has the ability to secrete TGF-beta, as well as the ability to respond to TGF-beta via the presence of TGF-beta receptors on the cell surface. Consequently, gain or loss of function of the TGF-beta pathway and its components are known to lead to a variety of diseases, including cancer. In epithelial cells, TGF-beta functions as a tumor suppressor, where it inhibits proliferation, induces apoptosis, and mediates differentiation. Conversely, in other contexts, TGF-beta promotes tumor progression through increasing tumor cell invasion and metastasis. Thus, TGF-beta can have opposing roles, likely dependent, in part, on whether the cancer is early or late stage. The effects of TGF-beta on tumor suppression and promotion are not limited to the tumor cell itself; rather, these effects can also be mediated through the stroma and the immune system. The dichotomous role of TGF-beta in cancer highlights our need to understand the contextual effects of this cytokine to better guide patient selection for the use of anti-TGF-beta therapies currently in clinical trials. Clin Cancer Res; 18( 17); 4514-21. (C)2012 AACR.