Detection of therapeutical effects by anti-EGFR therapy alone and in combination with chemotherapeutics against human squamous cell carcinomas of the head and neck using microarray techniques

MH Hambek, MD

University of Frankfurt Medical School, Frankfurt / Main, Hessen Germany

The use of monoclonal antibodies against the epidermal growth factor receptor of human squamous cell carcinomas of the head and neck has yet been evaluated in a few clinical studies. Remission of tumors could be demonstrated. However, in several cases this therapy does not inhibit tumor growth. Furthermore standard chemotherapy as well does not lead to tumor growth inhibition in all cases. Therefore new methods have to be defined for identification of non-responders to adjuvant therapeutical strategies. Hence, we are using the nude mice model to evaluate therapeutical response of xenotransplanted human tumors. We applicated on 2 days per week the monoclonal anti-EGFR antibody EMD 72000 to NMRI nude mice xenografted with the Detroit 562 squamous cell carcinoma cell line. Furthermore docetaxel was applicated to the same mice alone and in combination with the antibody. We used a observation time of 6-8 weeks. After that time tumors were taken from the mice to make further analysis. First we differentiated between tumors that did respond to therapy and tumors growing further on. Using microarray techniques we were able to identify different clusters of genes expressed in each therapeutic group as well as in case of therapeutical resistance. We also were able to show significant differences of tumor gene expression in case of long and short time therapy. Extremely significant differences in gene expression were related to cell cycle regulations, growth factors and cell to cell interactions. The results of our studies may influence decisions for the clinical use of adjuvant chemotherapeutics in head and neck tumor treatment.

KEY WORDS: chemosensitivity head and neck tumors monoclonal antibodies microarrays.

For more information, contact

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 2.