Resistance pathways relevant to insulin-like growth factor-1 receptor-targeted therapy

A. W. Hendrickson, P. Haluska

Research output: Contribution to journalReview articlepeer-review

37 Scopus citations

Abstract

The dysregulation of insulin-like growth factor (IGF) signaling has been implicated as a critical contributor to malignant transformation, proliferation, survival, migration and resistance to anticancer therapies. As a result, IGF signaling has become an attractive target for the development of novel anticancer agents, and a large number of compounds, including blocking antibodies and tyrosine kinase inhibitors targeting the key signaling kinase of the IGF system, the IGF-1 receptor (IGF-1R), are in preclinical and clinical development. Although most tumors express the IGF-1R, expression alone is unlikely to be sufficient for sensitivity to IGF-targeted treatment. An understanding of the IGF signaling system and its downstream effectors is important, as this information will allow appropriate molecular markers of sensitivity to be determined, thus providing the rationale for combining IGF-1R blockade with other therapies to overcome resistance. This review highlights some of the preclinical and early clinical data on determinants of sensitivity to IGF targeting in human cancers, and reviews the rationale for targeting other tyrosine kinases, such as the insulin receptor and members of the EGFR family, to overcome intrinsic resistance to targeted IGF-1R therapy.

Original languageEnglish (US)
Pages (from-to)1032-1040
Number of pages9
JournalCurrent Opinion in Investigational Drugs
Volume10
Issue number10
StatePublished - Oct 1 2009

Keywords

  • Epithelial-to-mesenchymal transition
  • ErbB receptor
  • Hsp90
  • IGF-1
  • IGF-2
  • Insulin receptor
  • Tyrosine kinase inhibitor
  • mAb inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery

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