Insulin and insulin-like growth factor signalling in neoplasia

Abstract

Insulin and insulin-like growth factor (IGF) signalling systems are ancient and involve regulation of physiology in ways beyond their well-known medically recognized roles concerning regulation of carbohydrate metabolism and growth. There is substantial experimental and clinical evidence that cancer cells express insulin and IGF1 receptors, and that these receptors are important activators of the Akt and mitogen-activated protein kinase signalling networks in neoplastic tissue. Population studies provide substantial direct and circumstantial evidence that cancer risk and cancer prognosis are influenced by IGF1 and insulin levels. Preclinical evaluation of drug candidates that target IGF1 and/or insulin signalling has revealed antineoplastic activity. At least 10 different drug candidates are being evaluated in clinical trials; early results have justified expansion of clinical trial programmes. Energy metabolism is an important topic in cancer research. IGF1 and insulin might have roles, along with other regulators, in mediating effects of perturbations of whole organism energy balance (for example, dietary excess, caloric restriction and exercise) on cellular energy physiology.