SMAD2 and cancer: These findings are significant because these SMAD2/3-activating ligands, particularly activin A and activin B, are elevated in many chronic conditions where muscle wasting is observed, including cancer, sepsis, lung disease, and heart disease (Michel et al., 2003; Yndestad et al., 2004, 2009; Loumaye et al., 2015, 2017).