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Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells

Cunningham, Matthew and Thomas, Hilary and Christopher, Marks and Margaret, Green and Zhen, Fan and Helmout, Modjtahedi (2008) Co-targeting the EGFR and IGF-IR with anti-EGFR monoclonal antibody ICR62 and the IGF-IR tyrosine kinase inhibitor NVP-AEW541 in colorectal cancer cells. International Journal of Oncology, 33 (5). pp. 1107-1113. ISSN 1019-6439

Abstract

The aberrant expression of the epidermal growth factor receptor (EGFR) has been reported in a wide range of epithelial tumours. In some studies, co-expression of insulin-like growth factor receptor-I (IGF-IR) have been associated with resistance to the EGFR inhibitors. Here, we investigated the sensitivity of a panel of human colorectal tumour cell lines, including two newly established lines Colo2 and Colo13, to treatment with anti-EGFR mAb ICR62 and IGF-IR tyrosine
kinase inhibitor NVP-AEW541 alone and in combination. We also determined the association between the expression levels
of EGFR and IGF-IR with their responses to ICR62 and/or NVP-AEW541. In contrast to DiFi cells, which contained high levels of EGFR but lower level of IGF-IR, the remaining 11 colorectal tumour cells expressed low levels of both EGFR and IGF-IR and such cells were relatively resistant to ICR62 or NVP-AEW-541 when used alone. Interestingly, compared to the results with the single agent, the effect of combination
of NVP-AEW541 and ICR62 was found to be additive on inhibiting the growth of Colo13, CCL235, CCL244 cells but
antagonistic in other (CCL218) cells. While overexpression
of the EGFR seems to be associated with response to ICR62,
no clear correlation was found between the expression levels
of EGFR and IGF-IR, or the levels of phosphorylated EGFR and response to treatment with NVP-AEW541, in single or
combination setting with ICR62. Our results suggest that
combining EGFR and IGF-IR inhibitors may enhance antitumour response in a fraction of colorectal cancer cells and warrants further study in colorectal cancer.

Item Type: Article
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Additional Information: Archiving status unclear?
Keywords: epidermal growth factor receptor; insulin-like growth factor receptor-I; ICR62; NVP-AEW541; colorectal cancer
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Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2538

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