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...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 January 2019
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| In: |
International journal of molecular sciences
Year: 2019, Volume: 20, Issue: 2 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms20020295 |
| Online Access: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3390/ijms20020295 Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/20/2/295 
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| Author Notes: | Sabine Heublein, Sabina Page, Doris Mayr, Elisa Schmoeckel, Fabian Trillsch, Frederik Marmé, Sven Mahner, Udo Jeschke and Aurelia Vattai |
| Summary: | 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. |
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| Item Description: | Gesehen am 23.01.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms20020295 |