IGF1R and Hyperinsulinemia: To enhance the effects of inhibiting IGF-1R, investigators have proposed the addition of chemotherapy to improve the potency of targeting IGF-1R.90 The combination of hormonal therapy plus an anti-IGF-1R moAb, e.g., ganitumab in metastatic breast cancer was one of the promising therapeutic strategies; unfortunately, hyperglycemia and hyperinsulinemia were major obstacles for the development of this drug.33 As discussed, IR is an essential component of the IGF-1R network, and IGF-1R mAb do not completely block its activation.