Targeted therapy of the insulin-like growth factor-1 receptor in cancer.
Recently, significant progress has been made towards understanding the pathogenesis of cancer from the molecular standpoint. To this end, a growing number of approaches are being exploited for the identification and validation of new therapeutic targets suitable for potent and specific intervention. The type 1 insulin-like growth factor receptor (IGF-1R) system has recently become the focus of major attention in the arena of cancer research. The involvement of the receptor and its downstream signaling cascades in the carcinogenesis process makes this system an excellent target for potential cancer therapy. Indeed, advances in the understanding of the molecular mechanisms behind IGF-1R activation have led to the discovery of agents designed selectively for targeting IGF-1R. The potential application of these inhibitors is currently under intense clinical investigation. This review describes the biology of IGF-1R particularly from a cancer perspective. The attempts to develop effective IGF-1R antagonists are discussed comprehensively with special emphasis on antibodies and small tyrosine kinase inhibitors.
Paz
Keren
K
Department of Tumor Biology, ImClone Systems Incorporated, New York, NY 10014, USA. keren.paz@imclone.com
Hadari
Yaron R
YR
D000818:Animals; D019138:Antibodies, Blocking; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D019138:Antibodies, Blocking; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1