[The role of insulin-like growth factors (IGF) in cell division processes and in malignancy].
Extensive research is being carried out to identify the role of insulin-like growth factor (IGF) in cellular development and tumorigenesis. There is substantial experimental and clinical evidence now that IGF and the related signalling pathways have important roles in regulating cellular proliferation, promoting cellular differentiation and anti-apoptotic effect. Significant amount of IGF is produced locally by neoplastic tissue, which gets into the circulation and adds to the naturally liver-generated and circulating amount. The IGF binding proteins (IGFBP) modulate the bioavailability of IGFs. Upon ligand binding to the receptor, the intrinsic tyrosine kinase activity initiates the phosphatidylinositol-3-kinase (PI3-K) and p38 mitogen activated protein kinase (MAPK) pathway; these have a summon effect on cell cycle. The ligand and the receptor biosynthesis are reviewed, as well as the signal transduction system and the IGF' role in neoplasm. Finally, the therapeutic modalities are surveyed with the preclinical drug's main features.
Vasas
Péter
P
Division of Surgery and Interventional Science, Royal Free & University College Medical School, University College London, London. vasasdr@gmail.com
Winslet
Marc C
MC
Shi
Yu Yang
YY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D002455:Cell Division; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D019869:Phosphatidylinositol 3-Kinases; D011505:Protein-Tyrosine Kinases; D020929:Mitogen-Activated Protein Kinase Kinases