Abstract
Introduction: Pharmacological targeting of the tyrosine kinase receptor HER2 with the monoclonal antibody trastuzumab has dramatically changed the outlook of HER2-positive breast cancer patients. However, HER2 is part of a more complex biological network that, when deregulated, plays a central role in sustaining the cancer phenotype. These interactions account for primary or acquired resistance to drugs that hit a single biological target, like trastuzumab. Several preclinical models suggest that simultaneous targeting of crucial metabolic pathways has the potential to circumvent or delay the onset of resistance phenomena in HER2-positive breast cancer cells. Areas covered: This review describes the rationale and results of clinical trials using biologically targeted agents in HER2-positive breast cancer patients. Single drugs that hit multiple targets and cocktails of biologically targeted agents are considered, whereas combinations with chemotherapy are not addressed. Expert opinion: Most of the studies using biological agents to hit multiple targets in HER2-positive breast cancer patients confirm that resistance to single-agent HER2-targeting can be overcome. Further developments will include combination of multi-targeting strategies with chemotherapy in patients with earlier-stage disease. In addition, it is possible that newer molecular predictive factors may allow a more rationale choice of the most appropriate targeting for each individual patient.
Original language | English |
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Pages (from-to) | 549-565 |
Number of pages | 17 |
Journal | Expert Opinion on Pharmacotherapy |
Volume | 12 |
Issue number | 4 |
DOIs | |
Publication status | Published - Mar 2011 |
Keywords
- Breast cancer
- Endocrine therapy
- HDAC inhibitors
- HER2
- HSP90 inhibitors
- IGF-1R
- Lapatinib
- mTOR inhibitors
- Neratinib
- Pazopanib
- Pertuzumab
- Trastuzumab
ASJC Scopus subject areas
- Pharmacology (medical)
- Pharmacology