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Targeting ligand-activated ErbB2 signaling inhibits breast and prostate tumor growth
Open accessAbstract
ErbB2 is a ligand-less member of the ErbB receptor family that functions as a coreceptor with EGFR, ErbB3, and ErbB4. Here, we describe an approach to target ErbB2's role as a coreceptor using a monoclonal antibody, 2C4, which sterically hinders ErbB2's recruitment into ErbB ligand complexes. Inhibition of ligand-dependent ErbB2 signaling by 2C4 occurs in both low- and high-ErbB2-expressing systems. Since the ErbB3 receptor contains an inactive tyrosine kinase domain, 2C4 is very effective in blocking heregulin-mediated ErbB3-ErbB2 signaling. We demonstrate that the in vitro and in vivo growth of several breast and prostate tumor models is inhibited by 2C4 treatment.
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“It is likely that also heregulin-driven tumors lacking HER2 amplification may benefit from HER2-directed therapies [92, 95, 96]”
From Primary and acquired resistance to EGFR-targeted therapies in colorectal cancer: impact on future treatment strategies (2014) · cites this paper as [96]
In the citing paper
“This is consistent with data showing that trastuzumab is unable to block ligand-induced HER2-containing heterodimers (Agus et al., 2002).”
From ERBB Receptors: From Oncogene Discovery to Basic Science to Mechanism-Based Cancer Therapeutics (2014) · cites this paper as Agus et al., 2002
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Metadata
- Authors
- Agus, D. B., Akita, R. W., Fox, W. D., Lewis, G. D., Higgins, B., Pisacane, P. I., Lofgren, J. A., Tindell, C., Evans, D. P., Maiese, K., Scher, H. I., & Sliwkowski, M. X.
- Affiliations
- Cedars-Sinai Medical Center (US)
- Genentech (US)
- Memorial Sloan Kettering Cancer Center (US)
- Corresponding author
- Sliwkowski, Mark X
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 2
- Issue
- 2
- Pages
- 127-137
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2014457594
- Cited by
- 873
- References
- 83
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 21 · 2023: 38 · 2022: 21 · 2021: 21 · 2020: 28 · 2019: 29 · 2018: 27 · 2017: 24 · 2016: 38 · 2015: 48 · 2014: 69 · 2013: 59 · 2012: 51
- FWCI
- 16.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- PepsiCo
- Topics
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- ERBB2, HER2, HER3, neuregulin-1, ErbB receptor family, breast cancer, prostate cancer, tumor growth inhibition, tyrosine kinase inhibitors
- MeSH terms
- Androgens, Animals, Antibodies, Monoclonal, Antineoplastic Agents, Breast Neoplasms, Cell Division, Female, Humans, Ligands, Male, Neoplasm Transplantation, Prostatic Neoplasms, Protein Binding, RNA, Messenger, Time Factors, Transplantation, Heterologous, Tumor Cells, Cultured, Signal Transduction, Gene Expression Regulation, Neoplastic, Erb-b2 Receptor Tyrosine Kinases, Neuregulin-1, Receptor, ErbB-3, Mice
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