Development of IGF-IR Inhibitors in Pediatric Sarcomas.
For approximately two decades, the insulin-like growth factor (IGF) has been implicated in the pathogenesis of numerous pediatric malignancies, including osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma. In the past, major toxicities have limited the clinical development of IGF-targeted therapies. However, recent interest has been heightened by the availability of increasingly specific small molecules and antibodies directed at IGF-I receptor. Preclinical data using these inhibitors against xenograft models of pediatric sarcomas, coupled with responses in adults with Ewing sarcoma, have generated significant excitement about the clinical potential of this class of drugs and have driven the rapid development of numerous clinical trials now under way. This article reviews the preclinical data and the ongoing clinical trials, as well as issues regarding the further development of these drugs specifically for pediatric malignancies.
Kolb
E Anders
EA
Alfred I. duPont Hospital for Children, Nemours Center for Childhood Cancer Research, 1600 Rockland Road, Wilmington, DE 19803, USA. eakolb@nemours.org
Gorlick
Richard
R
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D008954:Models, Biological; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D017526:Receptor, IGF Type 1