IGF-1R as an anti-cancer target--trials and tribulations.
- Author:
Helen X CHEN
1
;
Elad SHARON
Author Information
- Publication Type:Journal Article
- MeSH: Antibodies, Monoclonal; immunology; therapeutic use; Antineoplastic Agents; therapeutic use; Drug Combinations; Humans; Insulin-Like Growth Factor I; antagonists & inhibitors; Insulin-Like Growth Factor II; antagonists & inhibitors; Molecular Targeted Therapy; Neoplasms; therapy; Protein Kinase Inhibitors; therapeutic use; Receptor, IGF Type 1; antagonists & inhibitors; immunology; Sarcoma, Ewing; therapy; Signal Transduction
- From:Chinese Journal of Cancer 2013;32(5):242-252
- CountryChina
- Language:English
- Abstract: Type I insulin-like growth factor receptor (IGF-1R) has long been recognized for its role in tumorigenesis and growth, but only recently have the tools for targeting the IGF pathway become available. More than 10 IGF/IGF-1R inhibitors have entered clinical trials, and these belong to three main classes: (1) monoclonal antibodies against IGF-1R, (2) monoclonal antibodies against IGF-1R ligands (IGF-1 and IGF-2), and (3) IGF-1R tyrosine kinase inhibitors. These IGF-1R-targeting agents share common effects on IGF-1R signaling but differ in mechanisms of action, spectrum of target inhibition, and pharmacological features. Clinical activity of IGF-1R inhibitors has been demonstrated with sustained responses in a small number of patients with select tumor types, such as Ewing sarcoma and thymoma. However, many large clinical trials involving patients with adult tumors, including non-small cell lung cancer, breast cancer, and pancreatic cancer, failed to show clinical benefit in the overall patient population. Possible reasons for failure include the complexity of the IGF-1R/insulin receptor system and parallel growth and survival pathways, as well as a lack of patient selection markers. While IGF-1R remains a valid target for selected tumor types, identification of predictive markers and rational combinations will be critical to success in future development.
