Targeting TGF-β signal transduction for fibrosis and cancer therapy

Transforming growth factor beta (TGF-beta) 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-beta 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-beta 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-beta and its downstream molecules in the progression of fibrosis and cancers, therapeutics targeting TGF-beta signaling appears to be a promising strategy. However, due to potential systemic cytotoxicity, the development of TGF-beta therapeutics has lagged. In this review, we summarized the biological process of TGF-beta, with its dual role in fibrosis and tumorigenesis, and the clinical application of TGF-beta targeting therapies.

Automated summary

TGF-beta plays essential roles in early embryonic development, organogenesis, immune regulation, tissue repair, and adult homeostasis. Its involvement in fibrosis and cancer is complex and context-dependent, showing both inhibitory and promoting effects. Therapeutics targeting TGF-beta signaling hold promise in treating fibrosis and cancer, although the development is hindered by potential systemic cytotoxicity.