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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2015

01-10-2015 | Review

Non-HER2 signaling pathways activated in resistance to anti-HER2 therapy in breast cancer

Authors: Adela Madrid-Paredes, Marisa Cañadas-Garre, Antonio Sánchez-Pozo, Miguel Ángel Calleja-Hernández

Published in: Breast Cancer Research and Treatment | Issue 3/2015

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Abstract

HER2 receptor is overexpressed approximately in 20 % of human breast cancer (BC) and is a poor prognostic factor. Although therapies targeting this receptor have improved the prognosis of this cancer, up to 62 % patients treated with these drugs experiment progression during the first year of treatment. Some molecular mechanisms have been proposed to be responsible for this resistance, such as activation of alternative signaling pathways (through ERBB receptors and non-ERBB receptors or increased expression of ligands and alterations in HER2 signaling components). In this article, we will review the influence of genetic markers in non-HER2 signaling pathways investigated to date as cause of resistance to HER2-targeted drugs in HER2-positive BC patients. GRB7, included in the 17q12 amplicon, has been associated to poor prognosis in BC patients. Biomarkers like EPHAR and SRC, have demonstrated clinical relevance and prognostic value in HER2-positive BC patients. Non-invasive biomarkers, such as elevated IGF1 serum levels have been revealed as interesting biomarkers to be considered as predictors of trastuzumab clinical outcomes in BC patients. However, the prognostic value of most of the biomarkers investigated to date, such as HER3, IGF1R, PIK3CA, or AKT1 cannot be fully established yet, since results have not been conclusive.
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Metadata
Title
Non-HER2 signaling pathways activated in resistance to anti-HER2 therapy in breast cancer
Authors
Adela Madrid-Paredes
Marisa Cañadas-Garre
Antonio Sánchez-Pozo
Miguel Ángel Calleja-Hernández
Publication date
01-10-2015
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2015
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-015-3578-x

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