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  • Opinion
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Targeting the ERBB family in cancer: couples therapy

Abstract

The ERBB family of receptor tyrosine kinases has a central role in the tumorigenesis of many types of solid tumour. Various therapeutics targeting these receptors have been approved for the treatment of several cancers. Considerable preclinical data have shown that the administration of two inhibitors against an individual ERBB family member — particularly epidermal growth factor receptor (EGFR) or ERBB2 — leads to markedly higher antitumour activity than the administration of single agents. This Opinion article describes the preclinical and clinical performance of these dual-targeting approaches, discusses the key mechanisms that mediate their increased efficacy and highlights areas for ongoing investigation.

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Figure 1: EGFR and ERBB2 structure and therapeutic targets.
Figure 2: Enhanced antitumour mechanisms mediated by dual EGFR therapy.
Figure 3: Dual antibody therapy increases EGFR degradation.
Figure 4: Dual EGFR therapy overcomes TKI resistance.

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Acknowledgements

T.G.J.'s work on ERBB family inhibitors is supported by funding from the National Health and Medical Research Council of Australia (grant numbers 1012020 and 1028552) and the Victorian Government's Operational Infrastructure Support Program. T.G.J. is a recipient of a Clinical Fellowship from the Victorian Cancer Agency. The authors thank D. Dadley-Moore for help with editing the manuscript.

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Correspondence to Terrance G. Johns.

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T.G.J. has received research support from Pfizer and Amgen in the area of EGFR therapeutics. N.T. has received funding from and is a consultant for Roche, which markets erlotinib. M.W.P. is employed by Symphogen, which developed Sym004.

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Tebbutt, N., Pedersen, M. & Johns, T. Targeting the ERBB family in cancer: couples therapy. Nat Rev Cancer 13, 663–673 (2013). https://doi.org/10.1038/nrc3559

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