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Nuclear ErbB-2: a Novel Therapeutic Target in ErbB-2-Positive Breast Cancer?
- Source :
-
Hormones & cancer [Horm Cancer] 2019 Jun; Vol. 10 (2-3), pp. 64-70. Date of Electronic Publication: 2019 Jan 17. - Publication Year :
- 2019
-
Abstract
- 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.
- Subjects :
- Antineoplastic Agents therapeutic use
Apoptosis
Biomarkers
Biomarkers, Tumor metabolism
Breast Neoplasms drug therapy
Cell Nucleus metabolism
Cell Survival
Drug Resistance, Neoplasm
Female
Humans
Neoplasm Metastasis
Phosphatidylinositol 3-Kinases metabolism
Proto-Oncogene Proteins c-akt metabolism
Signal Transduction
Treatment Outcome
Breast Neoplasms metabolism
Molecular Targeted Therapy
Receptor, ErbB-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1868-8500
- Volume :
- 10
- Issue :
- 2-3
- Database :
- MEDLINE
- Journal :
- Hormones & cancer
- Publication Type :
- Academic Journal
- Accession number :
- 30656558
- Full Text :
- https://doi.org/10.1007/s12672-018-0356-3