Different hypotheses have been developed to explain their weak efficacy in thyroid carcinomas including: (i) the persistent activation of an IGF-2-IR-A autocrine loop favoring cancer progression [6,105], (ii) IGF-IR crosstalk with other RTKs [51], compensatory intracellular signaling causing loss of therapeutic efficacy [106] and (iii) molecular alterations in RTK downstream targets (e.g., RAS or B-RAF) driving cell growth regardless of IGF inhibition [33]. This evidence concerns the gene BRAF and thyroid gland carcinoma.