In late stage cancer, tumors such as melanomas, gliomas, and breast cancer have maintained a functional TGF-β receptor/SMAD pathway, but are resistant to the tumor suppressive effects of TGF-β due to loss of function mutation in tumor suppressor genes and/or acquiring oncogenic mutations, such as in the PI3K/AKT, RAS/MAPK pathway components [31]. This evidence concerns the gene TGFB1 and breast carcinoma.