Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines
<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development:...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-12-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://www.molecular-cancer.com/content/11/1/91 |
| _version_ | 1818835297925857280 |
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| author | Cavazzoni Andrea Alfieri Roberta R Cretella Daniele Saccani Francesca Ampollini Luca Galetti Maricla Quaini Federico Graiani Gallia Madeddu Denise Mozzoni Paola Galvani Elena La Monica Silvia Bonelli Mara Fumarola Claudia Mutti Antonio Carbognani Paolo Tiseo Marcello Barocelli Elisabetta Petronini Pier Giorgio Ardizzoni Andrea |
| author_facet | Cavazzoni Andrea Alfieri Roberta R Cretella Daniele Saccani Francesca Ampollini Luca Galetti Maricla Quaini Federico Graiani Gallia Madeddu Denise Mozzoni Paola Galvani Elena La Monica Silvia Bonelli Mara Fumarola Claudia Mutti Antonio Carbognani Paolo Tiseo Marcello Barocelli Elisabetta Petronini Pier Giorgio Ardizzoni Andrea |
| author_sort | Cavazzoni Andrea |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.</p> <p>Results</p> <p>In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity <it>in vitro</it>. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone.</p> <p>Conclusion</p> <p>Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both <it>in vitro</it> and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.</p> |
| first_indexed | 2024-12-19T02:48:29Z |
| format | Article |
| id | doaj.art-92f8f69964fc485bb048388b83f8c67a |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-19T02:48:29Z |
| publishDate | 2012-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-92f8f69964fc485bb048388b83f8c67a2022-12-21T20:38:46ZengBMCMolecular Cancer1476-45982012-12-011119110.1186/1476-4598-11-91Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell linesCavazzoni AndreaAlfieri Roberta RCretella DanieleSaccani FrancescaAmpollini LucaGaletti MariclaQuaini FedericoGraiani GalliaMadeddu DeniseMozzoni PaolaGalvani ElenaLa Monica SilviaBonelli MaraFumarola ClaudiaMutti AntonioCarbognani PaoloTiseo MarcelloBarocelli ElisabettaPetronini Pier GiorgioArdizzoni Andrea<p>Abstract</p> <p>Background</p> <p>The epidermal growth factor receptor (EGFR) is an established target for anti-cancer treatment in different tumour types. Two different strategies have been explored to inhibit this pivotal molecule in epithelial cancer development: small molecules TKIs and monoclonal antibodies. ErbB/HER-targeting by monoclonal antibodies such as cetuximab and trastuzumab or tyrosine-kinase inhibitors as gefitinib or erlotinib has been proven effective in the treatment of advanced NSCLC.</p> <p>Results</p> <p>In this study we explored the potential of combining either erlotinib with cetuximab or trastuzumab to improve the efficacy of EGFR targeted therapy in EGFR wild-type NSCLC cell lines. Erlotinib treatment was observed to increase EGFR and/or HER2 expression at the plasma membrane level only in NSCLC cell lines sensitive to the drug inducing protein stabilization. The combined treatment had marginal effect on cell proliferation but markedly increased antibody-dependent, NK mediated, cytotoxicity <it>in vitro</it>. Moreover, in the Calu-3 xenograft model, the combination significantly inhibited tumour growth when compared with erlotinib and cetuximab alone.</p> <p>Conclusion</p> <p>Our results indicate that erlotinib increases surface expression of EGFR and/or HER2 only in EGFR-TKI sensitive NSCLC cell lines and, in turns, leads to increased susceptibility to ADCC both <it>in vitro</it> and in a xenograft models. The combination of erlotinib with monoclonal antibodies represents a potential strategy to improve the treatment of wild-type EGFR NSCLC patients sensitive to erlotinib.</p>http://www.molecular-cancer.com/content/11/1/91Lung cancerEGFRErlotinibCetuximabADCC |
| spellingShingle | Cavazzoni Andrea Alfieri Roberta R Cretella Daniele Saccani Francesca Ampollini Luca Galetti Maricla Quaini Federico Graiani Gallia Madeddu Denise Mozzoni Paola Galvani Elena La Monica Silvia Bonelli Mara Fumarola Claudia Mutti Antonio Carbognani Paolo Tiseo Marcello Barocelli Elisabetta Petronini Pier Giorgio Ardizzoni Andrea Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines Molecular Cancer Lung cancer EGFR Erlotinib Cetuximab ADCC |
| title | Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines |
| title_full | Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines |
| title_fullStr | Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines |
| title_full_unstemmed | Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines |
| title_short | Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines |
| title_sort | combined use of anti erbb monoclonal antibodies and erlotinib enhances antibody dependent cellular cytotoxicity of wild type erlotinib sensitive nsclc cell lines |
| topic | Lung cancer EGFR Erlotinib Cetuximab ADCC |
| url | http://www.molecular-cancer.com/content/11/1/91 |
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