Overlaps between the Insulin and IGF-I receptor in cancer

Dysregulation of the insulin growth factor (IGF) system is implicated in various aspects of cancer. Notably, the physiological signaling specificity existing between insulin and insulin-like growth factors I and II (IGFs) is often disrupted in cancer by various mechanisms. These may include overexpression of IGFs and of IGF-I receptors (IGF-IR), aberrant expression of insulin receptor isoform A, and appearance of atypical receptors that bind both insulin and IGFs. Enhanced cross talk between insulin and the IGF-I receptors may also result from insulin resistance and chronic hyperinsulinemia, newly recognized risk factors for cancer. All these factors associated with reduced signaling specificity between insulin and IGFs may also activate unbalanced intracellular signaling more strongly coupled to protumoral biological effects than to metabolic effects. A better knowledge of the molecular mechanisms involved may have profound implications in cancer prevention and therapy.