期刊
ENDOCRINE-RELATED CANCER
卷 23, 期 12, 页码 T243-T257出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-16-0360
关键词
nuclear ErbB-2; breast cancer growth; metastasis; response to anti-ErbB-2 therapies; ErbB-2 transcriptional activity
资金
- National Agency of Scientific Promotion of Argentina (ANPCyT) [IDB/PICT 2012-668, PID 2012-066]
- Nelia and Amadeo Barletta Foundation from Switzerland
Approximately 15-20% of breast cancers (BC) show either membrane overexpression of ErbB-2 (MErbB-2), a member of the ErbBs family of receptor tyrosine kinases, or ERBB2 gene amplification. Until the development of MErbB-2-targeted therapies, this BC subtype, called ErbB-2-positive, was associated with increased metastatic potential and poor prognosis. Although these therapies have significantly improved overall survival and cure rates, resistance to available drugs is still a major clinical issue. In its classical mechanism, MErbB-2 activates downstream signaling cascades, which transduce its effects in BC. The fact that ErbB-2 is also present in the nucleus of BC cells was discovered over twenty years ago. Also, compelling evidence revealed a non-canonical function of nuclear ErbB-2 as a transcriptional regulator. As a deeper understanding of nuclear ErbB-2 actions would be crucial to the disclosure of its role as a biomarker and a target of therapy in BC, we will here review its function in BC, in particular, its role in growth, metastatic spreading and response to currently available MErbB-2-positive BC therapies.
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