Journal article
The paradoxical functions of EGFR during breast cancer progression
Signal transduction and targeted therapy, Vol.2(1), p.16042
01/01/2017
DOI: 10.1038/sigtrans.2016.42
PMCID: PMC5397119
PMID: 28435746
Abstract
The epidermal growth factor receptor (EGFR) is one of the most well-studied signaling pathways in cancer progression. As a result, numerous therapeutics including small-molecule inhibitors and monoclonal antibodies have been developed to target this critical oncogenic driver. Several of these EGFR inhibitors (EGFRi) have been evaluated in metastatic breast cancer, as high-level EGFR expression in primary tumors correlates with the highly aggressive basal-like phenotype and predicts for poor patient prognosis. Surprisingly, these trials have been unanimously unsuccessful at improving patient outcomes. Numerous factors, such as lack of proper patient selection may have contributed to the failure of these trials. However, recent findings suggest that there are fundamental changes in EGFR signaling that take place during primary tumor invasion, dissemination and ultimate metastasis of breast cancer cells. Herein, we review the outcomes of EGFR-targeted clinical trials in breast cancer and explore our current understanding of EGFR signaling within primary mammary tumors and how these events are altered in the metastatic setting. Overall, we put forth the hypothesis that fundamental changes in EGFR signaling between primary and metastatic tumors, a process we term the 'EGFR paradox,' contribute to the clinically observed inherent resistance to EGFRi. Furthermore, this hypothesis introduces the possibility of utilizing EGFR agonism as a potential therapeutic approach for the treatment of metastatic breast cancer.
Details
- Title: Subtitle
- The paradoxical functions of EGFR during breast cancer progression
- Creators
- Remah Ali - Purdue University West LafayetteMichael K. Wendt - Purdue University West Lafayette
- Resource Type
- Journal article
- Publication Details
- Signal transduction and targeted therapy, Vol.2(1), p.16042
- DOI
- 10.1038/sigtrans.2016.42
- PMID
- 28435746
- PMCID
- PMC5397119
- NLM abbreviation
- Signal Transduct Target Ther
- ISSN
- 2095-9907
- eISSN
- 2059-3635
- Publisher
- Springer Nature
- Number of pages
- 7
- Grant note
- R00CA166140 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R00CA166140 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) METavivor Foundation
- Language
- English
- Date published
- 01/01/2017
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984460329302771
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