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Med Sci Monit. 2002 Dec;8(12):BR521-6.

Co-targeting HER2/ErbB2 and insulin-like growth factor-1 receptors causes synergistic inhibition of growth in HER2-overexpressing breast cancer cells.

Author information

1
Department of Oncology, McGill University, Montréal, QC, Canada. ame.camirand@mail.mcgill.ca

Abstract

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.

PMID:
12503030
[Indexed for MEDLINE]

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