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Int. J. Mol. Sci. 2019, 20(2), 295; https://doi.org/10.3390/ijms20020295

Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer

1
Department of Obstetrics and Gynecology, Ludwig-Maximilians University of Munich, University Hospital, 81377 Munich, Germany
2
Department of Obstetrics and Gynecology, University of Heidelberg, 69117 Heidelberg, Germany
3
Department of Pathology, Ludwig-Maximilians University of Munich, 81377 Munich, Germany
*
Author to whom correspondence should be addressed.
Received: 26 October 2018 / Revised: 17 December 2018 / Accepted: 24 December 2018 / Published: 12 January 2019
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Abstract

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. View Full-Text
Keywords: Gatipotuzumab; Tamoxifen; ovarian cancer; 4-Hydroxy-Tamoxifen (4-OHT); survival Gatipotuzumab; Tamoxifen; ovarian cancer; 4-Hydroxy-Tamoxifen (4-OHT); survival
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Heublein, S.; Page, S.; Mayr, D.; Schmoeckel, E.; Trillsch, F.; Marmé, F.; Mahner, S.; Jeschke, U.; Vattai, A. Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer. Int. J. Mol. Sci. 2019, 20, 295.

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