Abstract
Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) can contribute to tumor development and -progression through their effects on cell proliferation, inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase inhibitors are currently in clinical use for the treatment of several types of cancer. However, primary and acquired resistance to these agents often occurs and thereby limits the clinical efficacy of monospecific targeted therapy. Results from both in vitro and in vivo studies indicate that cross-talk between EGFR and IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review describes the interface between the EGFR and IGF-1R signaling networks and the implications of the extensive cross-talk between these two receptor systems for cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors (GPCR) or downstream signaling molecules. This multi-layered cross-talk and its involvement in the induction of resistance to targeted therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R signaling as promising novel therapeutic approaches.
Keywords: Epidermal growth factor receptor, insulin-like growth factor-1 receptor, cross-talk, cancer therapy, dual targeting, resistance
Current Cancer Drug Targets
Title: Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy
Volume: 9 Issue: 6
Author(s): J. van der Veeken, S. Oliveira, R. M. Schiffelers, G. Storm, P.M.P. van Bergen en Henegouwen and R. C. Roovers
Affiliation:
Keywords: Epidermal growth factor receptor, insulin-like growth factor-1 receptor, cross-talk, cancer therapy, dual targeting, resistance
Abstract: Both the epidermal growth factor receptor (EGFR) and the insulin-like growth factor-1 receptor (IGF-1R) can contribute to tumor development and -progression through their effects on cell proliferation, inhibition of apoptosis, angiogenesis, anchorage-independent growth and tumor-associated inflammation. EGFR-targeting monoclonal antibodies and small molecule tyrosine kinase inhibitors are currently in clinical use for the treatment of several types of cancer. However, primary and acquired resistance to these agents often occurs and thereby limits the clinical efficacy of monospecific targeted therapy. Results from both in vitro and in vivo studies indicate that cross-talk between EGFR and IGF-1R can lead to acquired resistance against EGFR-targeted drugs. This review describes the interface between the EGFR and IGF-1R signaling networks and the implications of the extensive cross-talk between these two receptor systems for cancer therapy. EGFR and IGF-1R interact on multiple levels, either through a direct association between the two receptors, by mediating the availability of each others ligands, or indirectly, via common interaction partners such as G protein coupled receptors (GPCR) or downstream signaling molecules. This multi-layered cross-talk and its involvement in the induction of resistance to targeted therapies provide a clear rationale for dual targeting of EGFR and IGF-1R. We discuss several (potential) strategies to simultaneously inhibit EGFR and IGF-1R signaling as promising novel therapeutic approaches.
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Cite this article as:
Veeken van der J., Oliveira S., Schiffelers M. R., Storm G., Henegouwen van Bergen en P.M.P. and Roovers C. R., Crosstalk Between Epidermal Growth Factor Receptor- and Insulin-Like Growth Factor-1 Receptor Signaling: Implications for Cancer Therapy, Current Cancer Drug Targets 2009; 9 (6) . https://dx.doi.org/10.2174/156800909789271495
DOI https://dx.doi.org/10.2174/156800909789271495 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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