1. Hitting multiple targets in HER2-positive breast cancer: proof of principle or therapeutic opportunity?
- Author
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Geuna E, Milani A, Redana S, Rossi V, Valabrega G, Aglietta M, and Montemurro F
- Subjects
- Animals, Breast Neoplasms pathology, Clinical Trials as Topic, Drug Resistance, Neoplasm, Female, Humans, Neoplasm Staging, Receptor, ErbB-2 metabolism, Antineoplastic Agents pharmacology, Breast Neoplasms drug therapy, Drug Delivery Systems
- 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.
- Published
- 2011
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