GH1 and Insulin resistance: In addition to these direct effects of GH on the tumor biology, two indirect but major effects of GH lead further towards detrimental prognoses: (i) hepatic production of >75% of the circulating, potent mitogen and anti-cancer target IGF1, which also promotes a therapy resistant and invasive cancer phenotype (32), and (ii) increasing insulin resistance by exerting a diabetogenic effect, known since the 1930s (33).