The insulin-like growth factor system and sarcomas

Bart Rikhof*, Steven de Jong, Albert J. H. Suurmeijer, Coby Meijer, Winette T. A. van der Graaf

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

113 Citations (Scopus)

Abstract

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-IR), 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 (C) 2008 Pathological Society of Great Britain and Ireland. Published by lohn Wiley & Sons, Ltd.

Original languageEnglish
Pages (from-to)469-482
Number of pages14
JournalJOURNAL OF PATHOLOGY
Volume217
Issue number4
DOIs
Publication statusPublished - Mar-2009

Keywords

  • sarcoma
  • soft-tissue
  • bone
  • insulin-like growth factor
  • insulin-like growth factor receptor type 1
  • insulin receptor
  • targeted therapy
  • FACTOR-I-RECEPTOR
  • GASTROINTESTINAL STROMAL TUMORS
  • ISLET-CELL TUMOR
  • SMOOTH-MUSCLE TUMORS
  • HORMONE-RELEASING HORMONE
  • FACTOR-BINDING PROTEINS
  • SOFT-TISSUE SARCOMAS
  • OF-THE-LITERATURE
  • EWINGS-SARCOMA
  • IGF-II

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