Cargando…
Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation
Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuxi...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563086/ https://www.ncbi.nlm.nih.gov/pubmed/23383403 http://dx.doi.org/10.3389/fonc.2013.00013 |
_version_ | 1782258146469740544 |
---|---|
author | Wachsberger, Phyllis Rachelle Lawrence, Richard Yaacov Liu, Yi Rice, Barbara Daskalakis, Constantine Dicker, Adam P. |
author_facet | Wachsberger, Phyllis Rachelle Lawrence, Richard Yaacov Liu, Yi Rice, Barbara Daskalakis, Constantine Dicker, Adam P. |
author_sort | Wachsberger, Phyllis Rachelle |
collection | PubMed |
description | Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolomide (TMZ), and radiation therapy (RT). Methods and Materials: In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR) and the other overexpressing EGFRvIII (U87EGFRvIII). Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing. Conclusion: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant. |
format | Online Article Text |
id | pubmed-3563086 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-35630862013-02-04 Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation Wachsberger, Phyllis Rachelle Lawrence, Richard Yaacov Liu, Yi Rice, Barbara Daskalakis, Constantine Dicker, Adam P. Front Oncol Oncology Purpose: EGFR amplification and mutation (i.e., EGFRvIII) are found in 40% of primary GBM tumors and are believed to contribute to tumor development and therapeutic resistance. This study was designed to investigate how EGFR mutational status modulates response to multimodality treatment with cetuximab, an anti-EGFR inhibitor, the chemotherapeutic agent, temozolomide (TMZ), and radiation therapy (RT). Methods and Materials: In vitro and in vivo experiments were performed on two isogenic U87 GBM cell lines: one overexpressing wildtype EGFR (U87wtEGFR) and the other overexpressing EGFRvIII (U87EGFRvIII). Results: Xenografts harboring EGFRvIII were more sensitive to TMZ alone and TMZ in combination with RT and/or cetuximab than xenografts expressing wtEGFR. In vitro experiments demonstrated that U87EGFRvIII-expressing tumors appear to harbor defective DNA homologous recombination repair in the form of Rad51 processing. Conclusion: The difference in sensitivity between EGFR-expressing and EGFRvIII-expressing tumors to combined modality treatment may help in the future tailoring of GBM therapy to subsets of patients expressing more or less of the EGFR mutant. Frontiers Media S.A. 2013-02-04 /pmc/articles/PMC3563086/ /pubmed/23383403 http://dx.doi.org/10.3389/fonc.2013.00013 Text en Copyright © 2013 Wachsberger, Lawrence, Liu, Rice, Daskalakis and Dicker. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Oncology Wachsberger, Phyllis Rachelle Lawrence, Richard Yaacov Liu, Yi Rice, Barbara Daskalakis, Constantine Dicker, Adam P. Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title | Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title_full | Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title_fullStr | Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title_full_unstemmed | Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title_short | Epidermal Growth Factor Receptor Mutation Status and Rad51 Determine the Response of Glioblastoma to Multimodality Therapy with Cetuximab, Temozolomide, and Radiation |
title_sort | epidermal growth factor receptor mutation status and rad51 determine the response of glioblastoma to multimodality therapy with cetuximab, temozolomide, and radiation |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563086/ https://www.ncbi.nlm.nih.gov/pubmed/23383403 http://dx.doi.org/10.3389/fonc.2013.00013 |
work_keys_str_mv | AT wachsbergerphyllisrachelle epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation AT lawrencerichardyaacov epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation AT liuyi epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation AT ricebarbara epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation AT daskalakisconstantine epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation AT dickeradamp epidermalgrowthfactorreceptormutationstatusandrad51determinetheresponseofglioblastomatomultimodalitytherapywithcetuximabtemozolomideandradiation |