SMAD3 and cancer: Our previous work dissected the pleiotropic effects of TGF‐β1 signaling, therefore, revealing the importance of Smad3 in the bone‐marrow‐derived TME.[6] TGF‐β1/Smad3 signaling can induce CAF generation from several distinct sources, including epithelial and endothelial cells.[30, 31, 32, 33] The pathogenic mechanism of the Smad3‐TME is still largely unknown; particularly, in CAF regulation, a better understanding may uncover new therapeutic targets for cancer.