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Breast Cancer Research
Published in: Breast Cancer Research 1/2020

Open Access 01-12-2020 | Breast Cancer | Research article

Simultaneous targeting of HER family pro-survival signaling with Pan-HER antibody mixture is highly effective in TNBC: a preclinical trial with PDXs

Authors: Tejaswini P. Reddy, Dong S. Choi, Ann C. Anselme, Wei Qian, Wen Chen, Johan Lantto, Ivan D. Horak, Michael Kragh, Jenny C. Chang, Roberto R. Rosato

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

The human epidermal growth factor receptor (HER) family, notably EGFR, is overexpressed in most triple-negative breast cancer (TNBC) cases and provides cancer cells with compensatory signals that greatly contribute to the survival and development of resistance in response to therapy. This study investigated the effects of Pan-HER (Symphogen, Ballerup, Denmark), a novel mixture of six monoclonal antibodies directed against members of the HER family EGFR, HER2, and HER3, in a preclinical trial of TNBC patient-derived xenografts (PDXs).

Methods

Fifteen low passage TNBC PDX tumor samples were transferred into the right mammary fat pad of mice for engraftment. When tumors reached an average size of 100–200 mm3, mice were randomized (n ≥ 6 per group) and treated following three 1-week cycles consisting of three times/week intraperitoneal (IP) injection of either formulation buffer (vehicle control) or Pan-HER (50 mg/kg). At the end of treatment, tumors were collected for Western blot, RNA, and immunohistochemistry analyses.

Results

All 15 TNBC PDXs were responsive to Pan-HER treatment, showing significant reductions in tumor growth consistent with Pan-HER-mediated tumor downmodulation of EGFR and HER3 protein levels and significantly decreased activation of associated HER family signaling pathways AKT and ERK. Tumor regression was observed in five of the models, which corresponded to those PDX tumor models with the highest level of HER family activation.

Conclusions

The marked effect of Pan-HER in numerous HER family-dependent TNBC PDX models justifies further studies of Pan-HER in TNBC clinical trials as a potential therapeutic option.
Appendix
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Metadata
Title
Simultaneous targeting of HER family pro-survival signaling with Pan-HER antibody mixture is highly effective in TNBC: a preclinical trial with PDXs
Authors
Tejaswini P. Reddy
Dong S. Choi
Ann C. Anselme
Wei Qian
Wen Chen
Johan Lantto
Ivan D. Horak
Michael Kragh
Jenny C. Chang
Roberto R. Rosato
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-020-01280-z

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