Role of the IGF axis in prostate cancer progression

The major issue currently being faced in the management of prostate cancer is the inability to distinguish between indolent prostate tumors that will not present clinically from more aggressive and metastatic prostate cancers that will impact on men's lives. Only a small proportion of prostate cancers can be accounted for by unmistakable hereditary cancer syndromes and the predominant contribution to the progression of most sporadic cancers is thought to be environmental, with nutrition having the greatest influence. Population studies have clearly implicated metabolic factors as contributors to disease progression and poor response to therapy. It is well established that the IGF system is key in regulating growth and metabolism and mediates the effects of nutrition on these processes. It consists of two ligands (IGF-I and IGF-II), two receptors [type 1 IGF-IR and IGF-II/mannose 6-phosphate receptor], and six high affinity IGF-binding proteins (IGFBP-1 to -6). This review provides evidence from in vitro, in vivo, clinical and epidemiology studies that indicates an important role for the IGF axis in the development of prostate cancer and the likely role that it plays in mediating the effects of nutrition on disease progression. We suggest that the IGF axis is central to understanding how lifestyle impacts on prostate cancer and we highlight this by describing numerous strategies being developed to target this axis.