Insulin-like growth factor receptor inhibitors: baby or the bathwater?

J Natl Cancer Inst. 2012 Jul 3;104(13):975-81. doi: 10.1093/jnci/djs258. Epub 2012 Jul 3.


The success of targeted therapies for cancer is undisputed; strong preclinical evidence has resulted in the approval of several new agents for cancer treatment. The type I insulin-like growth factor receptor (IGF1R) appeared to be one of these promising new targets. Substantial population and preclinical data have all pointed toward this pathway as an important regulator of tumor cell biology. Although early results from clinical trials that targeted the IGF1R showed some evidence of response, larger randomized phase III trials have not shown clear clinical benefit of targeting this pathway in combination with conventional strategies. These disappointing results have resulted in the discontinuation of several anti-IGF1R programs. However, the conduct of these trials has brought to the forefront several important factors that need to be considered in the conduct of future clinical trials. The need to develop biomarkers, a clearer understanding of insulin receptor function, and defining rational combination regimens all require further consideration. In this commentary, the current state of IGF1R inhibitors in cancer therapy is reviewed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Body Height
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / prevention & control
  • Breast Neoplasms / surgery
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Clinical Trials as Topic
  • Disease Progression
  • Early Termination of Clinical Trials
  • Endocrine Disruptors*
  • Evidence-Based Medicine
  • Female
  • Human Growth Hormone / administration & dosage
  • Human Growth Hormone / metabolism
  • Humans
  • Hyperinsulinism / complications
  • Hypophysectomy*
  • Immunoglobulins, Intravenous
  • Insulin-Like Growth Factor I / metabolism*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism*
  • Ovariectomy
  • Receptor, IGF Type 1 / antagonists & inhibitors*
  • Receptor, IGF Type 1 / metabolism*
  • Risk Factors
  • Signal Transduction
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Endocrine Disruptors
  • Immunoglobulins, Intravenous
  • Human Growth Hormone
  • cixutumumab
  • Insulin-Like Growth Factor I
  • ganitumab
  • Receptor, IGF Type 1
  • figitumumab