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Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer
Anti-tumor efficacy of Gatipotuzumab, a therapeutic antibody targeting Tumor-Associated Mucin-1 (TA-MUC1), in relapsed ovarian cancer (OC) appeared to be rather heterogeneous. Whether adding a second anti-neoplastic drug may augment response towards Gatipotuzumab, has not been elucidated so far. Sin...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359481/ https://www.ncbi.nlm.nih.gov/pubmed/30642093 http://dx.doi.org/10.3390/ijms20020295 |
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author | Heublein, Sabine Page, Sabina Mayr, Doris Schmoeckel, Elisa Trillsch, Fabian Marmé, Frederik Mahner, Sven Jeschke, Udo Vattai, Aurelia |
author_facet | Heublein, Sabine Page, Sabina Mayr, Doris Schmoeckel, Elisa Trillsch, Fabian Marmé, Frederik Mahner, Sven Jeschke, Udo Vattai, Aurelia |
author_sort | Heublein, Sabine |
collection | PubMed |
description | Anti-tumor efficacy of Gatipotuzumab, a therapeutic antibody targeting Tumor-Associated Mucin-1 (TA-MUC1), in relapsed ovarian cancer (OC) appeared to be rather heterogeneous. Whether adding a second anti-neoplastic drug may augment response towards Gatipotuzumab, has not been elucidated so far. Since it is known that anti-MUC1 antibodies may alter estrogen receptor activity in breast cancer, this potential interplay was investigated in OC. The correlation between TA-MUC1, estrogen receptors (ERs) and another 12 protein markers as well as their correlation with clinico-pathological parameters in 138 ovarian cancer cases was studied. Finally, Gatipotuzumab and 4-Hydroxy-TTamoxifen (4-OHT) as well as the combination of both was tested for its impact on cell viability in COV318, OV-90, OVCAR-3, and SKOV-3 cells. A strong positive correlation between TA-MUC1 and ERs was detected in OC tissue. Those cases missing ERs but staining positive for TA-MUC1 had significantly reduced overall survival. The combination of 4-OHT and Gatipotuzumab significantly reduced cell viability and was more effective than treatment with Gatipotuzumab alone. Co-stimulation with Gatipotuzumab enhanced the efficacy of 4-OHT in OVCAR-3 and SKOV-3. The data suggest an interplay of TA-MUC1 and ERs in OC. Whether the combination of Gatipotuzumab and TTamoxifen may enhance efficacy of either of the two drugs in vivo, or may even translate into a clinically relevant benefit over the respective monotherapies, remains to be investigated. |
format | Online Article Text |
id | pubmed-6359481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63594812019-02-06 Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer Heublein, Sabine Page, Sabina Mayr, Doris Schmoeckel, Elisa Trillsch, Fabian Marmé, Frederik Mahner, Sven Jeschke, Udo Vattai, Aurelia Int J Mol Sci Article Anti-tumor efficacy of Gatipotuzumab, a therapeutic antibody targeting Tumor-Associated Mucin-1 (TA-MUC1), in relapsed ovarian cancer (OC) appeared to be rather heterogeneous. Whether adding a second anti-neoplastic drug may augment response towards Gatipotuzumab, has not been elucidated so far. Since it is known that anti-MUC1 antibodies may alter estrogen receptor activity in breast cancer, this potential interplay was investigated in OC. The correlation between TA-MUC1, estrogen receptors (ERs) and another 12 protein markers as well as their correlation with clinico-pathological parameters in 138 ovarian cancer cases was studied. Finally, Gatipotuzumab and 4-Hydroxy-TTamoxifen (4-OHT) as well as the combination of both was tested for its impact on cell viability in COV318, OV-90, OVCAR-3, and SKOV-3 cells. A strong positive correlation between TA-MUC1 and ERs was detected in OC tissue. Those cases missing ERs but staining positive for TA-MUC1 had significantly reduced overall survival. The combination of 4-OHT and Gatipotuzumab significantly reduced cell viability and was more effective than treatment with Gatipotuzumab alone. Co-stimulation with Gatipotuzumab enhanced the efficacy of 4-OHT in OVCAR-3 and SKOV-3. The data suggest an interplay of TA-MUC1 and ERs in OC. Whether the combination of Gatipotuzumab and TTamoxifen may enhance efficacy of either of the two drugs in vivo, or may even translate into a clinically relevant benefit over the respective monotherapies, remains to be investigated. MDPI 2019-01-12 /pmc/articles/PMC6359481/ /pubmed/30642093 http://dx.doi.org/10.3390/ijms20020295 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Heublein, Sabine Page, Sabina Mayr, Doris Schmoeckel, Elisa Trillsch, Fabian Marmé, Frederik Mahner, Sven Jeschke, Udo Vattai, Aurelia Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title | Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title_full | Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title_fullStr | Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title_full_unstemmed | Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title_short | Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer |
title_sort | potential interplay of the gatipotuzumab epitope ta-muc1 and estrogen receptors in ovarian cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359481/ https://www.ncbi.nlm.nih.gov/pubmed/30642093 http://dx.doi.org/10.3390/ijms20020295 |
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