期刊
JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA
卷 14, 期 1, 页码 55-66出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10911-009-9116-x
关键词
Breast neoplasms; erbB-2 receptor; Monoclonal antibodies; Protein-tyrosine kinases; Cancer stem cells
Although the development of trastuzumab and lapatinib has improved the outlook for women with HER-2 positive breast cancer, resistance to HER-2 targeted therapy is a growing clinical dilemma. Recent evidence indicates that the HER-2 pathway may play an important role in the maintenance of cancer stem cells (CSCs). The success of HER-2 targeted therapies may, in part, be explained by their direct activity against HER-2 positive CSCs. Our understanding of the mechanisms involved in resistance to trastuzumab, including loss or blockade of the trastuzumab binding site, activation of alternative signaling pathways, and induction of epithelial-mesenchymal transition (EMT), suggests that CSCs may be at the root of resistance of HER-2 targeted therapy. A variety of novel HER-2 targeted approaches have demonstrated promising preliminary clinical activity. Future clinical trials should involve the integration of technologies to assess the impact of novel HER-2 targeted therapies on HER-2 positive CSCs.
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