Other analyses on in vivo and in vitro models of CRC reported that 5-FU is able to stimulate the activation of SMAD-3 and the related TGF-β pathway in chemoresistant cells inducing changes in the surrounding tumor microenvironment (i.e., increased vascularization) and cell mechanisms of death and proliferation [55]. The gene discussed is SMAD3; the disease is colorectal carcinoma.