Dual inhibition of ErbB1 (EGFR/HER1) and ErbB2 (HER2/neu).
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.
Reid
Alison
A
Royal Marsden Hospital, The Institute of Cancer Research, Centre for Cancer Therapeutics, Downs Road, Sutton, Surrey SM2 5PT, UK.
Vidal
Laura
L
Shaw
Heather
H
de Bono
Johann
J
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017321:Clinical Trials, Phase I as Topic; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D018773:Genes, erbB-1; D018734:Genes, erbB-2; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases