Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer
AbstractAnti-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
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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.
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. International Journal of Molecular Sciences. 2019; 20(2):295.Chicago/Turabian Style
Heublein, Sabine; Page, Sabina; Mayr, Doris; Schmoeckel, Elisa; Trillsch, Fabian; Marmé, Frederik; Mahner, Sven; Jeschke, Udo; Vattai, Aurelia. 2019. "Potential Interplay of the Gatipotuzumab Epitope TA-MUC1 and Estrogen Receptors in Ovarian Cancer." Int. J. Mol. Sci. 20, no. 2: 295.
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