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  • Title: Combining trastuzumab and cetuximab combats trastuzumab-resistant gastric cancer by effective inhibition of EGFR/ErbB2 heterodimerization and signaling.
    Author: Zheng L, Tan W, Zhang J, Yuan D, Yang J, Liu H.
    Journal: Cancer Immunol Immunother; 2014 Jun; 63(6):581-6. PubMed ID: 24668364.
    Abstract:
    The anti-ErbB2 antibody trastuzumab has currently been approved for ErbB2-positive gastric cancer. Despite the effectiveness of trastuzumab, resistance is common. Thus, there is an urgent need to overcome trastuzumab resistance. Here, we obtain a trastuzumab-resistant cell line, which is derived from the human gastric cancer NCI-N87 cell line, by modeling the development of acquired resistance in patients. Our data show that combining trastuzumab and cetuximab leads to a significant decrease in EGFR/ErbB2 heterodimers and signaling compared with either antibody alone, and the combination results in greater antitumor activity against the trastuzumab-resistant NCI-N87 cell line, both in vitro and in vivo, suggesting that a combined EGFR/ErbB2 inhibition may overcome trastuzumab resistance.
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