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Eur J Cancer. 2007 Feb;43(3):481-9. Epub 2007 Jan 8.

Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).

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  • 1Royal Marsden Hospital, The Institute of Cancer Research, Centre for Cancer Therapeutics, Downs Road, Sutton, Surrey SM2 5PT, UK.


Targeting of epidermal growth factor receptor (EGFR) and HER2 is a proven anti-cancer strategy. However, heterodimerisation, compensatory 'crosstalk' and redundancy exist in the ErbB network, and there is therefore a sound scientific rationale for dual inhibition of EGFR and HER2. Trials of approved agents in combination, for example trastuzumab and cetuximab, are underway. There is also a new generation of small molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mABs) that target two or more ErbB receptors. Lapatinib, a TKI of EGFR and HER2, has shown clinical benefit in trastuzumab refractory breast cancer and is poised for FDA approval. Other agents include BIBW-2992 and HKI-272, irreversible TKIs of EGFR and HER2, and pertuzumab, a heterodimerisation inhibitor of EGFR and HER2.

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