IGF-1R as an anti-cancer target--trials and tribulations / 癌症
Chinese Journal of Cancer
;
(12): 242-252, 2013.
Article
in English
| WPRIM
| ID: wpr-320591
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Sarcoma, Ewing
/
Therapeutics
/
Insulin-Like Growth Factor I
/
Insulin-Like Growth Factor II
/
Signal Transduction
/
Receptor, IGF Type 1
/
Therapeutic Uses
/
Protein Kinase Inhibitors
/
Drug Combinations
/
Allergy and Immunology
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Chinese Journal of Cancer
Year:
2013
Type:
Article
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