Bortezomib (PS-341, Velcade) increases the efficacy of trastuzumab (Herceptin) in HER-2-positive breast cancer cells in a synergistic manner.
- Cardoso, Fatima
- Durbecq, Virginie
- Laes, Jean-François
- Badran, Bassam
- Lagneaux, Laurence
- Bex, Françoise
- Desmedt, Christine
- Willard-Gallo, Karen
- Ross, Jeffrey S.
- Burny, Arsène
- Piccart-Gebhart, Martine
- Sotiriou, Christos
DOIAbstract
BACKGROUND: Preclinical and clinical studies have shown that the proteasome inhibitor bortezomib (PS341, Velcade) is highly effective when combined with chemotherapeutic agents. The value of trastuzumab (Herceptin) in HER-2-positive (3+ score by immunohistochemistry or fluorescence in situ hybridization positive) breast cancer is also known; however, the response rate is <40% for metastatic breast cancer. These two pharmacologic agents prevent nuclear factor-kappaB (NF-kappaB) activation and induce nuclear accumulation of the cyclin-dependent kinase inhibitor p27(kip1), suggesting that combining bortezomib with trastuzumab could increase trastuzumab efficacy. METHODS: Drug cytotoxicity, both individually and together, and drug effects on p2...
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