Targeting TGF-ß signal transduction for fibrosis and cancer therapy.

Transforming growth factor ß (TGF-ß) has long been identified with its intensive involvement in early embryonic development and organogenesis, immune supervision, tissue repair, and adult homeostasis. The role of TGF-ß in fibrosis and cancer is complex and sometimes even contradictory, exhibiting either inhibitory or promoting effects depending on the stage of the disease. Under pathological conditions, overexpressed TGF-ß causes epithelial-mesenchymal transition (EMT), extracellular matrix (ECM) deposition, cancer-associated fibroblast (CAF) formation, which leads to fibrotic disease, and cancer. Given the critical role of TGF-ß and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-ß signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-ß therapeutics has lagged. In this review, we summarized the biological process of TGF-ß, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-ß-targeting therapies.