Reduced levels of SMAD3 or loss of SMAD4 suppressed the function of TGF-β-induced expression of tumor suppressor genes, resulting in the expression of anti-apoptotic proteins Bcl2 and Bcl-W, and enhanced cancer cell survival to confer platinum-resistance in NSCLC and 5-FU resistance in CRC, respectively (Zhang et al., 2014; Vu et al., 2020). Here, SMAD4 is linked to colorectal carcinoma.