insulin-like growth factor system and sarcomas

• Published in: The Journal of pathology Vol. 217; no. 4; pp. 469 - 482
• Main Authors: Rikhof, Bart, de Jong, Steven, Suurmeijer, Albert JH, Meijer, Coby, van der Graaf, Winette TA
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.03.2009; Wiley
• Subjects: Antibodies, Monoclonal - therapeutic use; Biological and medical sciences; bone; Humans; Hypoglycemia - metabolism; Insulin - metabolism; insulin receptor; insulin-like growth factor; Insulin-Like Growth Factor II - metabolism; Insulin-Like Growth Factor II - secretion; insulin-like growth factor receptor type 1; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Neoplasm Proteins - metabolism; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Protein Precursors - metabolism; Protein Precursors - secretion; Receptors, Somatomedin - immunology; Receptors, Somatomedin - metabolism; sarcoma; Sarcoma - metabolism; Sarcoma - secretion; Signal Transduction - physiology; soft-tissue; Somatomedins - metabolism; targeted therapy; soft-tissue; Sarcoma; Targeted therapy; Malignant tumor; Osteoarticular system; Anatomic pathology; Insulin like growth factor; Treatment; insulin-like growth factor receptor type 1; Targeted drug; Soft tissue; insulin-like growth factor; Bone; Insulin receptor; Cancer; Hormonal receptor
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2499

Sarcomas are a diverse group of malignant mesenchymal tumours arising from bone and soft tissues. The identification of critical cellular signalling pathways in sarcomas is an important issue for the development of new targeted therapies. This review highlights the experimental and clinical evidence supporting the role of the insulin-like growth factor (IGF) signalling system in the cellular transformation and progression of several types of sarcoma, including rhabdomyosarcoma, synovial sarcoma, leiomyosarcoma, Ewing's sarcoma and osteosarcoma. Preclinical data suggest that the IGF system could be a promising target for therapy in these sarcomas. Currently, therapies interrupting IGF signalling have been or are being developed. In recent phase 1 clinical studies with humanized monoclonal antibodies directed against IGF receptor type 1 (IGF-1R), objective tumour responses were observed in several patients with Ewing's sarcoma, encouraging further clinical testing in Ewing's sarcoma and other sarcoma (sub)types. Moreover, the occasional occurrence of paraneoplastic hypoglycaemia as a result of the secretion of incompletely processed forms of pro-IGF-II by sarcomas is discussed. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.