Multifaceted TGF‐β signaling, a master regulator: From bench‐to‐bedside, intricacies, and complexities

Abstract Physiological embryogenesis and adult tissue homeostasis are regulated by transforming growth factor‐β (TGF‐β), an evolutionarily conserved family of secreted polypeptide factors, acting in an autocrine and paracrine manner. The role of TGF‐β in inflammation, 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, especially fibrosis and cancer, overexpressed TGF‐β causes extracellular matrix deposition, epithelial–mesenchymal transition, cancer‐associated fibroblast formation, and/or angiogenesis. In this review article, we have tried to dive deep into the mechanism of action of TGF‐β in inflammation, fibrosis, and carcinogenesis. As TGF‐β and its downstream signaling mechanism are implicated in fibrosis and carcinogenesis blocking this signaling mechanism appears to be a promising avenue. However, targeting TGF‐β carries substantial risk as this pathway is implicated in multiple homeostatic processes and is also known to have tumor‐suppressor functions. There is a need for careful dosing of TGF‐β drugs for therapeutic use and patient selection.