Insulin-like growth factor 1 receptor as a therapeutic target in ewing sarcoma: Lack of consistent upregulation or recurrent mutation and a review of the clinical trial literature Journal Article
| Authors: | O'neill, A.; Shah, N.; Zitomersky, N.; Ladanyi, M.; Shukla, N.; Uren, A.; Loeb, D.; Toretsky, J. |
| Article Title: | Insulin-like growth factor 1 receptor as a therapeutic target in ewing sarcoma: Lack of consistent upregulation or recurrent mutation and a review of the clinical trial literature |
| Abstract: | The insulin-like growth factor 1 receptor (IGF-1R) has been considered an important therapeutic target in Ewing sarcoma (ES), generating a need to identify the subset of patients most likely to respond to IGF-1R inhibitors. We assessed IGF-1R expression in ES cell lines and patient tumors to understand the variable clinical responses to anti-IGF-1R therapy. Using ligand-binding displacement, we measured between 13,000 and 40,000 receptors per cell in ES cell lines. We used ELISA to quantify IGF-1R in patient tumors, which expressed 4.8% ± 3.7 to 20.0% ± 0.2 of the levels in a positive control cell line overexpressing IGF-1R. Flow cytometry showed markedly reduced IGF-1R expression in ES cell lines compared to a standard positive control cell line. The IGF1R gene was sequenced in 47 ES tumor samples and 8 ES cell lines; only one tumor sample showed a nonsynonymous mutation, R1353H, in a region with low functional impact. Finally, we assessed IGF-1R pathway activity in the ES stem cell (ESSC) population, to characterize its potential for resistance to anti-IGF-1R therapy, using Luminex technology. We found no significant differences in IGF-1R pathway activity between ESSCs and the total cell population. Overall, our findings suggest that IGF-1R as a therapeutic target in this sarcoma may require reevaluation. © 2013 Alison O'Neill et al. |
| Journal Title: | Sarcoma |
| Volume: | 2013 |
| ISSN: | 1357-714X |
| Publisher: | Hindawi Publishing Corporation |
| Date Published: | 2013-01-01 |
| Start Page: | 450478 |
| Language: | English |
| DOI: | 10.1155/2013/450478 |
| PROVIDER: | scopus |
| PMCID: | PMC3569907 |
| PUBMED: | 23431249 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 April 2013" - "CODEN: SARCF" - "Source: Scopus" |
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