While TKIs are promising agents, their disruption of glucose homeostasis and other metabolic functions make them difficult to employ as long-term clinical strategies.70 There are three principle challenges associated with anti-IGF-1R hormonal therapy: (1) most of the anti-IGF-1R antibodies are reported to have minor responses,86 (2) the therapy targeting IGF-1R causes hyperglycemia due either to disruption of GH homeostasis or direct inhibition of IR by TKIs,87 and (3) chronic exposure to anti-IGF-1R might induce resistance. This evidence concerns the gene GH1 and Hyperglycemia.