To date, no definitive evidence suggests that activation of the insulin or IGF-1 receptor by itself can trigger the “benign versus malignant transformation switch.” In contrast, a more direct role in tumor progression has been demonstrated for IGF-II, which is often secreted by cancer cells and acts as a key autocrine/paracrine factor in the tumor microenvironment, promoting the angiogenic switch and malignant progression [24]. This evidence concerns the gene INS and cancer.