SMAD3 and colorectal cancer: Beyond the effect on radiotherapy, it should be noted that the TGF-β/SMAD3 pathway was also reported to be involved in the mechanism of resistance to chemotherapeutics, including 5-FU, in colorectal cancer by modulating TGF-β downstream effectors with pro-proliferative, and pro-metastatic and anti-apoptotic effects (Moon et al., 2015; Romano et al., 2016).