HER-2 Positive Breast Cancer: What Else Beyond Trastuzumab-Based Therapy?

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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HER-2 Positive Breast Cancer: What Else Beyond Trastuzumab-Based Therapy?



Anti-Cancer Agents in Medicinal Chemistry, 8(5): 488-496.

Author(s): Christian Widakowich, Phuong Dinh, Evandro de Azambuja, Ahmad Awada and Martine Piccart-Gebhart.

Affiliation: Department of Medicine, Medical Oncology Clinic, Institut Jules Bordet, Rue Heger-Bordet, 1, 1000 Brussels, Belgium.

Abstract

HER-2 is a tyrosine kinase receptor which is overexpressed in 20-25% of breast cancer patients and is associated with poor prognosis. Trastuzumab, a humanized monoclonal antibody directed against the HER-2 receptor, used alone or in combination with chemotherapy, has shown significant clinical benefit in improving survival in metastatic patients, as well as halving the recurrence rate and improving survival in early breast cancer. Even with these impressive results, the reality is that not all patients will benefit form this therapy, and in those who do, resistance to trastuzumab can often develop within 1 year of treatment initiation. Beyond trastuzumab therapy, a “second wave” of monoclonal antibodies and tyrosine kinase inhibitors has emerged. These drugs have variable properties including: 1) dual inhibition against EGFR and HER-2, such as lapatinib, HKI-272 and pertuzumab; 2) antiangiogenesis such as bevacizumab and pazopanib; 3) anti-mTOR action such as Temsirolimus; and 4) anti-Hsp90 such as 17-AAG. When used in combination with trastuzumab, or with cytotoxic chemotherapy, or as single agents, these new anti-HER-2 strategies bear the potential of arresting the tumorigenesis process. In this article, we present the current strategies in the treatment of breast cancer patients who overexpress HER-2, with particular focus on new tyrosine kinase inhibitors that can be used in combination with or after trastuzumab therapy.

Keywords:

Breast cancer, TKI, lapatinib, HKI-272, temsirolimus, HSP-90.



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Article Details

Volume: 8
Issue Number: 5
First Page: 488
Last Page: 496
Page Count: 9
DOI: 10.2174/187152008784533062
Price: $58
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