The effect of monoclonal antibody cetuximab (C225) in combination with tyrosine kinase inhibitor gefitinib (ZD1839) on colon cancer cell lines.

AIMS

The epidermal growth factor receptor (EGFR) is abnormally activated in many tumours. Two different categories of compounds targeting EGFR, monoclonal antibodies (mAbs) and low molecular weight tyrosine kinase inhibitors (TKIs), which target extracellular and intracellular domains of the receptor, respectively, have shown antitumour activity. We decided to explore whether the combined administration of cetuximab, a mAb, and gefitinib, a TKI, had superior antitumour activity than either agent given alone.

METHODS

We studied the effects of cetuximab alone, gefitinib alone and the combination of cetuximab and gefitinib in two colon cancer cell lines, HT-29 and LoVo. The effects of these two agents on cell proliferation and induction of apoptosis were evaluated.

RESULTS

Dose-dependent activity of cetuximab alone or gefitinib alone or the combination was observed for both colon cancer cell lines. In addition, the combined treatment with cetuximab and gefitinib resulted in a synergistic and more pronounced growth effect on cell proliferation and induction of apoptosis than either single-agent treatment.

CONCLUSIONS

Our findings suggest that combined treatment with distinct EGFR inhibitory agents can augment the antitumour response over that realised with a single EGFR inhibitor. New and tempting treatment strategies on the EGFR target consisting of a double hit with a mAb and a TKI may improve the therapeutic ratio for colorectal cancer in future clinical trials.