IGF-IR signaling in epithelial to mesenchymal transition and targeting IGF-IR therapy: overview and new insights

Mol Cancer. 2017 Jan 30;16(1):6. doi: 10.1186/s12943-016-0576-5.

Abstract

The insulin-like growth factor-I (IGF-I) signaling induces epithelial to mesenchymal transition (EMT) program and contributes to metastasis and drug resistance in several subtypes of tumors. In preclinical studies, targeting of the insulin-like growth factor-I receptor (IGF-IR) showed promising anti-tumor effects. Unfortunately, high expectations for anti-IGF-IR therapy encountered challenge and disappointment in numerous clinical trials. This review summarizes the regulation of EMT by IGF-I/IGF-IR signaling pathway and drug resistance mechanisms of targeting IGF-IR therapy. Most importantly, we address several factors in the regulation of IGF-I/IGF-IR-associated EMT progression that may be potential predictive biomarkers in targeted therapy.

Keywords: EMT; IGF-I; IGF-IR; Metastasis; Therapy.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Clinical Trials as Topic
  • Drug Resistance, Neoplasm* / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Receptor, IGF Type 1
  • Receptors, Somatomedin / metabolism*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • IGF1R protein, human
  • Receptors, Somatomedin
  • Receptor, IGF Type 1