title: Bidirectional Crosstalk between the Estrogen Receptor and Human Epidermal Growth Factor Receptor 2 Signaling Pathways in Breast Cancer: Molecular Basis and Clinical Implications.
abstract: The estrogen receptor (ER) and/or the human epidermal growth factor receptor 2 (HER2) signaling pathways are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. As a result, targeting these pathways provides the most effective therapies in appropriately selected patients. Nevertheless, resistance to both endocrine and anti-HER2 therapies occurs frequently and represents a major clinical challenge. Compelling preclinical and clinical evidence relates this treatment resistance to the presence of a complex bidirectional molecular crosstalk between the ER and HER2 pathways. As a consequence, treatment strategies targeting either pathway are associated with up-regulation of the other one, ultimately resulting in resistance to therapy. Therefore, a more promising strategy to prevent or overcome either endocrine or anti-HER2 resistance at least in some tumors is to combine targeted treatments that simultaneously block both signaling pathways. Many clinical trials exploring this strategy have shown positive results, and many more are currently ongoing. Future clinical trials with appropriate patient selection, based on biomarker evaluation of primary tumors and possibly of recurrent lesions, are warranted for the optimization of individualized therapeutic strategies.
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, University of Houston, College of Pharmacy, Houston, TX, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Giuliano
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, University of Houston, College of Pharmacy, Houston, TX, USA ; Department of Clinical Sciences and Administration, University of Houston, College of Pharmacy, Houston, TX, USA.
authors.forename: Meghana V
authors.initials: MV
authors.lastname: Trivedi
authors.affiliation: Lester and Sue Smith Breast Center, Baylor College of Medicine, University of Houston, College of Pharmacy, Houston, TX, USA ; Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, USA ; Margaret M. and Albert B. Alkek Department of Medicine, Baylor College of Medicine, Houston, TX, USA ; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Schiff
keywords: Crosstalk; Estrogen Receptor; HER2; Resistance