Inhibition of insulin-like growth factor receptor: end of a targeted therapy?

• Type of Material: Article
• Authors: Rathi Pillai, Emory University; Suresh Ramalingam, Emory University
• Language: English
• Date: 2013-02
• Publisher: AME Publications
• Publication Version: Final Published Version
• Copyright Statement: 2013 Translational lung cancer research.OpenAccessThis journal provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.
• Final Published Version (URL): http://dx.doi.org/10.3978/j.issn.2218-6751.2012.11.05
• Title of Journal or Parent Work: Translational Lung Cancer Research
• Volume: 2
• Issue: 1
• Start Page: 14
• End Page: 22
• Keywords: Insulin-like Growth Factor 1 (IGF-1); insulin-like growth factor 1 receptor (IGF-1R); epidermal growth factor receptor (EGFR); non-small cell lung cancer (NSCLC)
• Research Categories: Health Sciences, General; Health Sciences, Oncology

Abstract

The Insulin-like Growth Factor 1 (IGF-1) signaling pathway activates several downstream signals important to lung cancer development and survival. IGF-1R activation has been linked to cancer risk in epidemiological studies and tumorigenesis in preclinical models. Several inhibitors of the insulin-like growth factor 1 receptor (IGF-1R) have been tested in clinical trials. Despite promising data in early phase studies, most studies of IGF-1R antagonists in combination with chemotherapy or with epidermal growth factor receptor (EGFR) inhibitors in non-small cell lung cancer (NSCLC) yielded disappointing results. Biomarker studies of clinical trials have identified IGF-1 levels as a potential marker of sensitivity to IGF-1R inhibition. Further study will need to focus on selection of NSCLC patients most likely to benefit from the addition of IGF-1R antagonists to standard therapy and the development of rational strategies for combination therapy in NSCLC.