• Eur. J. Cancer · Feb 2007

    Review

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

    • Alison Reid, Laura Vidal, Heather Shaw, and Johann de Bono.
    • Royal Marsden Hospital, The Institute of Cancer Research, Centre for Cancer Therapeutics, Downs Road, Sutton, Surrey SM2 5PT, UK.
    • Eur. J. Cancer. 2007 Feb 1; 43 (3): 481-9.

    AbstractTargeting 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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