Dear Colleagues,

Insulin and the insulin receptor control glucose homeostasis, whereas insulin-like growth factors (IGF-1 and IGF-2) and their type I IGF receptor control neonatal and postnatal growth—so far so simple. However, the insulin receptor exists in two isoforms, one of which has higher affinity for IGFs. All three ligands can activate both receptors, which recruit the same adapter proteins to activate the same signal transduction pathways, notably the PI3-kinase/Akt pathway.

Preclinical and translation studies implicate the insulin and IGF signal transduction system in cancer, and powerful pharmaceutical agents have been developed. Antibodies against the receptors and ligands and competitive inhibitors of the receptor kinase domains have had activity in preclinical models and early phase trials. Phase III trials, however, failed.

Concurrently, the rise in obesity has led to increased presentation of and mortality from certain cancers. IGFs secreted by adipocytes may contribute to this. Obesity leads to insulin resistance, compensatory hyperinsulinemia, and eventually type II diabetes mellitus, and high insulin doses are required to overcome insulin resistance, but high plasma insulin levels are associated with cancer incidence. Metformin, which lowers insulin secretion, reduces cancer incidence. Strategies to reduce weight and insulin secretion have shown clinical benefit.

This Special Issue addresses contributions of the insulin and IGF signal transduction system to cancer development, progression, and therapeutic response. Questions include associations with increased cancer presentation and mortality, the importance of the two receptors, how activation of the PI3-kinase/Akt pathway affects oncogene-driven cancers and negative feedback from targeted intervention, and the role of de novo and acquired resistance in targeted, classic, and radiation therapies. Could patient selection, tumour-specific delivery, and combined therapies improve response?

Dr. Felicity E.B. May
Guest Editor

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• insulin-like growth factor
• insulin
• tyrosine kinase receptor
• PI3-kinase/Akt pathway
• negative feedback
• therapeutic resistance
• obesity
• hyperinsulinemia