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

MADERA, SANTIAGO; CORDO RUSSO, ROSALÍA I.; CHARREAU, EDUARDO H.; CHERVO, MARÍA F.; ELIZALDE, PATRICIA V.

Hormones and Cancer

Springer US

Año: 2019 vol. 10 p. 64 - 70

1868-8497

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.