BACKGROUND: The humanized anti-HER2 monoclonal antibody trastuzumab (Herceptin) 
is useful in the treatment of ErbB2-overexpressing breast cancers, but its 
efficiency is limited because development of resistance is common. In order to 
study the possibility of improving the efficacy of therapies directed against 
HER2/erbB2, we investigated the effects of co-targeting this receptor and the 
insulin-like growth factor 1 receptor (IGF-1R), a widely-expressed protein 
tyrosine kinase with important roles in suppression of apoptosis and stimulation 
of proliferation.
MATERIAL/METHODS: The experimental strategy involved combining trastuzumab 
treatment and reduction of IGF-1R signaling through incremental heat-induced 
expression of the dominant-negative IGF-1 receptor 486/STOP under the control of 
the heat-sensitive Drosophila HSP70 promoter, in HER2/erbB2-overexpressing 
MCF7her18 breast cancer cells.
RESULTS: Isobologram analysis of combinatorial treatment data revealed a strong 
synergistic interaction between trastuzumab treatment and the induction of the 
dominant-negative IGF-1R expression, resulting in potentiation of growth 
inhibition in transfected cancer cells.
CONCLUSIONS: These observations support the concept that simultaneously 
co-targeting tyrosine kinase receptors may be therapeutically useful, and 
provide a specific rationale for combining IGF-1R and HER2/erbB2 targeting 
strategies in anti-neoplastic approaches.