Nuclear ErbB-2: a Novel Therapeutic Target in ErbB-2-Positive Breast Cancer?

  • Rosalía I. Cordo RussoEmail author
  • María F. Chervo
  • Santiago Madera
  • Eduardo H. Charreau
  • Patricia V. ElizaldeEmail author


Membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbB family of receptor tyrosine kinases, occurs in 15–20% of breast cancers (BC) and constitutes a therapeutic target in this BC subtype (ErbB-2-positive). Although MErbB-2-targeted therapies have significantly improved patients’ clinical outcome, resistance to available drugs is still a major issue in the clinic. Lack of accurate biomarkers for predicting responses to anti-ErbB-2 drugs at the time of diagnosis is also an important unresolved issue. Hence, a better understanding of the ErbB-2 signaling pathway constitutes a critical task in the battle against BC. In its canonical mechanism of action, MErbB-2 activates downstream signaling pathways, which transduce its proliferative effects in BC. The dogma of ErbB-2 mechanism of action has been challenged by the demonstration that MErbB-2 migrates to the nucleus, where it acts as a transcriptional regulator. Accumulating findings demonstrate that nuclear ErbB-2 (NErbB-2) is involved in BC growth and metastasis. Emerging evidence also reveal a role of NErbB-2 in the response to available anti-MErbB-2 agents. Here, we will review NErbB-2 function in BC and will particularly discuss the role of NErbB-2 as a novel target for therapy in ErbB-2-positive BC.


Nuclear ErbB-2 Breast cancer Metastasis Response to ErbB-2-targeted therapies Transcriptional coactivator ErbB-2 signaling pathway 



We thank Mien-Chie Hung (MD Anderson Cancer Center, Houston, TX, USA) for his generous help and support during the course of our studies of ErbB-2 nuclear function. We are grateful to Valerie Paul Roux for her assistance in the preparation of the manuscript. We thank René Barón Foundation and Willliams Foundation for their institutional support.

Funding Information

This work was supported by IDB/PICT 2015–1587, IDB/PICT 2012-668, and PID 2012-066 grants from the National Agency of Scientific Promotion of Argentina (ANPCyT); by a grant from the Nelia and Amadeo Barletta Foundation from Switzerland; and by a grant from the National Institute of Cancer from Argentina, all of them awarded to PVE. RICR was awarded with an early career research grant from AJ Roemmers Foundation.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


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Authors and Affiliations

  1. 1.Laboratory of Molecular Mechanisms of CarcinogenesisInstituto de Biología y Medicina Experimental (IBYME), CONICETBuenos AiresArgentina

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