Smart prodrugs systems based on doxorubicin and other small molecules, targeting the protease activity of cathepsin B in tumor microenvironment have been demonstrated to be highly efficient in killing metastatic cancer cells while sparing normal cell (Dubowchik et al., 2002; Dubowchik et al., 1998; Zhong et al., 2013). This evidence concerns the gene CTSB and cancer.