BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) has been observed in a variety of epithelial tumours. The selective inhibition of the associated signalling pathway using monoclonal antibodies appears to be a promising therapeutic target. Individual differences in response rates, particularly against highly selective chemotherapeutic agents, underline the need for further research of the molecular basis of this process. Previously described resistance mechanisms are not able to explain all refractory responses. Several subgroups of the melanoma-associated antigens (MAGE) tumour antigens were described in connection with regulatory functions relating to the cell cycle and chemosensitivity. METHODS: In the present study, five cell lines of human squamous cell carcinomas were treated with cetuximab and panitumumab (0.01-100 μg/ml) over a period of 24 or 48 h. The efficacy of the agents used was measured dynamically using real-time cell analysis (RTCA). Subsequently, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by RT-qPCR. A correlation between chemosensitivity and MAGE-A expression was investigated. RESULTS: The tumour cell lines exhibited a very low overall response to the chemotherapy drugs. Only one cell line showed a cytostatic effect after treatment with cetuximab and panitumumab. This effect, however, was significant only for panitumumab. The expression of MAGE-A12 was significantly associated with greater efficacy of panitumumab. The expression of MAGE-A5 and -A8 was associated with poorer response rates after panitumumab treatment. Due to an insignificant effect of cetuximab on the number of viable cells, no correlation with the MAGE-A levels was observed. CONCLUSION: For the first time, these results show a correlation between the efficacies of EGFR inhibitors and various MAGE-A subgroups in the treatment of HNSCC. Determining the MAGE-A status could help to improve the success of anti-tumour drug therapy. In addition, evaluating MAGE-A levels might be an important tool in the development of patient-specific treatment protocols.
BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) has been observed in a variety of epithelial tumours. The selective inhibition of the associated signalling pathway using monoclonal antibodies appears to be a promising therapeutic target. Individual differences in response rates, particularly against highly selective chemotherapeutic agents, underline the need for further research of the molecular basis of this process. Previously described resistance mechanisms are not able to explain all refractory responses. Several subgroups of the melanoma-associated antigens (MAGE) tumour antigens were described in connection with regulatory functions relating to the cell cycle and chemosensitivity. METHODS: In the present study, five cell lines of humansquamous cell carcinomas were treated with cetuximab and panitumumab (0.01-100 μg/ml) over a period of 24 or 48 h. The efficacy of the agents used was measured dynamically using real-time cell analysis (RTCA). Subsequently, the expression levels of MAGE-A1, -A5, -A8, -A9, -A11 and -A12 were determined by RT-qPCR. A correlation between chemosensitivity and MAGE-A expression was investigated. RESULTS: The tumour cell lines exhibited a very low overall response to the chemotherapy drugs. Only one cell line showed a cytostatic effect after treatment with cetuximab and panitumumab. This effect, however, was significant only for panitumumab. The expression of MAGE-A12 was significantly associated with greater efficacy of panitumumab. The expression of MAGE-A5 and -A8 was associated with poorer response rates after panitumumab treatment. Due to an insignificant effect of cetuximab on the number of viable cells, no correlation with the MAGE-A levels was observed. CONCLUSION: For the first time, these results show a correlation between the efficacies of EGFR inhibitors and various MAGE-A subgroups in the treatment of HNSCC. Determining the MAGE-A status could help to improve the success of anti-tumour drug therapy. In addition, evaluating MAGE-A levels might be an important tool in the development of patient-specific treatment protocols.
Authors: Stefan Hartmann; Norbert Neckel; Axel Seher; Grit Mutzbauer; Roman C Brands; Christian Linz; Alexander C Kübler; Urs D A Müller-Richter Journal: Clin Oral Investig Date: 2015-08-23 Impact factor: 3.573
Authors: Till J Meyer; Stefan Hartmann; Gisela Wohlleben; Muna Brisam; Axel Seher; Alexander C Kübler; Bülent Polat; Urs D A Müller-Richter Journal: Mol Clin Oncol Date: 2018-01-19
Authors: Stefan Hartmann; Muna Brisam; Stephan Rauthe; Oliver Driemel; Roman C Brands; Andreas Rosenwald; Alexander C Kübler; Urs D A Müller-Richter Journal: Oncol Lett Date: 2016-08-03 Impact factor: 2.967
Authors: Stefan Hartmann; Leonie Zwick; Mario J J Scheurer; Andreas R Fuchs; Roman C Brands; Axel Seher; Hartmut Böhm; Alexander C Kübler; Urs D A Müller-Richter Journal: Clin Oral Investig Date: 2017-10-15 Impact factor: 3.573
Authors: Stefan Hartmann; Roman C Brands; Nora Küchler; Andreas Fuchs; Christian Linz; Alexander C Kübler; Urs D A Müller-Richter Journal: Oncol Lett Date: 2015-06-09 Impact factor: 2.967
Authors: Roman C Brands; Franziska Herbst; Stefan Hartmann; Axel Seher; Christian Linz; Alexander C Kübler; Urs D A Müller-Richter Journal: Clin Oral Investig Date: 2016-02-04 Impact factor: 3.573