The insulin-like growth factor system and sarcomas.
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.
Rikhof
Bart
B
Department of Medical Oncology, University Medical Centre Groningen, University of Groningen, The Netherlands. b.rikhof@int.umcg.nl
de Jong
Steven
S
Suurmeijer
Albert J H
AJ
Meijer
Coby
C
van der Graaf
Winette T A
WT
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D017451:Receptors, Somatomedin / Q000276:immunology / Q000378:metabolism*; D012509:Sarcoma / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013002:Somatomedins / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007328:Insulin; D009363:Neoplasm Proteins; D011498:Protein Precursors; D017451:Receptors, Somatomedin; D013002:Somatomedins; C066038:proinsulin-like growth factor II; D007335:Insulin-Like Growth Factor II