Abstract
The antibody trastuzumab and the tyrosine kinase inhibitor lapatinib are approved by the FDA for the treatment of HER2-overexpressing breast cancer. These anti-HER2 drugs are changing the natural history of HER2-overexpressing breast cancer. However, therapeutic resistance to trastuzumab or lapatinib, as either single-agents or in combination with chemotherapy in the metastatic setting, typically occurs within months of starting therapy. Several mechanisms of trastuzumab-resistance have been reported that include signaling from other HER receptors, signaling from receptor tyrosine kinases (RTKs) outside of the HER (ErbB) family, increased phosphatidylinositol-3-kinase signaling, and the presence of truncated forms of HER2. Mechanisms of resistance to lapatinib also point to increased phosphatidylinositol 3-kinase signaling as well as derepression/activation of compensatory survival pathways. In this review, we discuss how these models and mechanisms enhance our understanding of the clinical resistance to HER2-directed therapies.
Original language | English (US) |
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Pages (from-to) | 793-800 |
Number of pages | 8 |
Journal | Cancer Biology and Therapy |
Volume | 11 |
Issue number | 9 |
DOIs | |
State | Published - May 1 2011 |
Keywords
- Antibodies
- Drug resistance
- HER2 (ERBB2)
- Lapatinib
- Trastuzumab
- Tyrosine kinase inhibitors
ASJC Scopus subject areas
- Molecular Medicine
- Oncology
- Pharmacology
- Cancer Research