Establishment And Characterization Of The Mda-Mb-175 Breast Tumor Xenograft Model

Background: The MDA-MB-175 cell line is widely used in vitro for targeted drug development in breast cancers with ERBB 2/3 receptor and heregulin signaling. However, lack of an accessible, matched xenograft has limited in vivo analysis of potential therapies. To better utilize this cell line as a tool for receptor targeting drug development, we established the MDA-MB-175 xenograft model in athymic nude mice. The resulting model was characterized and compared with the parent line using immunohistochemistry and genomic analysis. In vivo studies were performed using the xenograft model comparing various ERBB2 and ERBB3-targeting agents. Materials and Methods: The MDA-MB-175 xenograft model was established and serially passaged in athymic nude mice for in vivo studies. Receptor expression was determined using immunohistochemistry and RNA in-situ hybridization and compared with the parent line. For the in vivo study of ERBB2/3 targeting therapies, trastuzumab, lapatinib, pertuzumab, T-DM1, and neratinib were evaluated as monotherapies, along with a trastuzumab/lapatinib combination group. Dosing was initiated on Day 0 and continued for four weeks at which time tumor regrowth was followed. The study was ended on Day 60 and drug response reported at Day 28 and Day 60 as %T/C values and %Tumor Regressions (%TR). Results: Immunohistochemistry on the cell line and model reported intensity values of (2+) for ERBB2 and ERBB3 receptor expression. In vivo the following %T/C were reported on Day 28: trastuzumab=50%,lapatinib=62%, pertuzumab= -96% (100% TR), T-DM1=-19% (50% TR), neratinib=-88% (100% TR) and trastuzumab/lapatinib=72%. Day 60 results reported regrowth in neratinib and T-DM1 groups. Conclusion: We have established a reproducible xenograft model of the MDA-MB-175 cell line that is sensitive to pertuzumab, T-DM1, and neratinib, but neither trastuzumab nor lapatinib alone or in combination in vivo. Citation Format: Michael J. Wick, Megan Groves, Alyssa Moriarty, Marcus Guerra, Melissa Rundle, Drew Rasco, Amita Patnaik, Anthony W. Tolcher, Kyriakos P. Papadopoulos. Establishment and characterization of the MDA-MB-175 breast tumor xenograft model [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A007.