Insulin-like growth factor (IGF) axis in cancerogenesis.

Determination of the role of insulin-like growth factor (IGF) family components in carcinogenesis of several human tumors is based on numerous epidemiological and pre-clinical studies, experiments in vivo and in vitro and on attempts at application of drugs affecting the IGF axis. Investigative hypotheses in original studies were based on biological functions manifested by the entire family of IGF (ligands, receptors, linking proteins, adaptor molecules). In the context of carcinogenesis the most important functions of IGF family involve intensification of proliferation and inhibition of cell apoptosis and effect on cell transformation through synthesis of several regulatory proteins. IGF axis controls survival and influences on metastases of cells. Interactions of IGF axis components may be of a direct or indirect nature. The direct effects are linked to activation of PI3K/Akt signaling pathway, in which the initiating role is first of all played by IGF-1 and IGF-1R. Activity of this signaling pathway leads to an increased mitogenesis, cell cycle progression, and protection against different apoptotic stresses. Indirect effects of the axis depend on interactions between IGF and other molecules important for cancer etiology (e.g. sex hormones, products of suppressor genes, viruses, and other GFs) and the style of life (nutrition, physical activity). From the clinical point of view, components of IGF system are first of all considered as diagnostic serous and/or tissue biomarkers of a given cancer, prognostic factors and attractive target of modern anti-tumor therapies. Several mechanisms in which IGF system components act in the process of carcinogenesis need to be clarified, mainly due to multifactorial etiology of the neoplasms. Pin-pointing of the role played in carcinogenesis by any single signaling pathway remains particularly difficult. The aim of this review is to summarize the current data of several epidemiological studies, experiments in vitro and on animal models, to increase our understanding of the complex role of IGF family components in the most common human cancers.