This is illustrated by the results of a study on a cohort of patients with a GIST, showing that the patients with a relatively high tumor load (i.e., total diameter >12 cm) exhibited significantly higher pretreatment plasma levels of IGF‐IIE [68–87] than subjects with a lower tumor load.59 Presumably, when a certain threshold level of big IGF‐II in the circulation is exceeded, the low affinity signaling via the IR‐B becomes increasingly important, which in particular causes insulin‐like metabolic changes. The gene discussed is IGF2; the disease is neoplasm.