The network of insulin and insulin-like growth factors in prostate cancer Introduction Prostate cancer is the most common type of cancer diagnosed among men. According to the American Cancer Society, approximately 200,000 new cases will be diagnosed and 29,000 men will die from prostate cancer in 20141. Local prostate tumors can be treated with surgery and/or radiotherapy. Metastatic disease, however, has fewer treatment options, especially for patients with castration-resistant prostate disease2. The androgens testosterone and DHT are the main growth factors responsible for the development and growth of the prostate. Other non-androgenic growth factors are also involved, such as insulin-like growth factors (IGFs) and insulin, which have been implicated in the progression of prostate cancer2. IGF is a potent mitogen in both normal and cancer cells, promoting cell cycle progression and DNA synthesis. Insulin carries out its classic metabolic actions in the prostate, also initiating proliferation and anti-apoptotic effects. IGF is secreted by the liver after growth hormone (GH) stimulation from the pituitary gland, commonly referred to as the IGF/GH axis. The IGF system consists of two ligands, IGF-1 and IGF-2, and two cell surface receptors IGF1R and IGF2R. IGFs bind to the IGF1R receptor, which is heterotetrameric with two alpha ligand-binding subunits and two transmembrane beta subunits. Binding of IGF induces autophosphorylation of beta subunits and activation of protein tyrosine kinase. IGFs also interact with six high-affinity IGF-binding proteins (IGFBPs) that modulate IGF activity through inhibition or activation. Multiple pathways can be activated following phosphorylation, including the MAPK and PI3K pathways, as well as a...... half of the article ...... Specific area covered by the articles The IGF axis is a complex system implicated in pathogenesis of prostate cancer, but the entire mechanism has not been clearly defined. Although IGF-1 and its receptor IGF1R are considered oncogenic in prostate cancer, the pathways involved have not been useful in terms of therapeutic potential. Here three different studies demonstrated new pathways and molecules associated with IGF signaling in prostate cancer. Cancerous and noncancerous prostate cells respond to IGF stimulation in very different ways, inducing proliferation and differentiation, respectively. This illustrates a clear difference in IGF signaling and potential avenues for targeted therapies. Since IGFs are necessary growth factors in various tissues, it may be useful to utilize the different signaling response in normal and cancer cells.