Mouse and cell line experiments demonstrate synergistic effects for lapatinib and trastuzumab-- Jeff Muise
Wednesday, March 17, 2010 (Last Updated: 03/18/2010)
WEDNESDAY, March 17 (HealthDay News) -- Lapatinib (Tykerb) and trastuzumab (Herceptin), two drugs already used in breast cancer treatment, are probably effective when used in combination against upper gastric cancers with the mutation for amplified expression of the human epidermal growth factor receptor 2 (HER2) protein, according to a study in the March 1 issue of Clinical Cancer Research.
Zev A. Wainberg, M.D., of the University of California in Los Angeles, and colleagues assessed levels of epidermal growth factor receptor (EGFR) and HER2 protein expression in 14 cell lines for human upper gastrointestinal cancer. The researchers exposed the cells to lapatinib, erlotinib (Tarceva), and trastuzumab individually and in combination and evaluated the cancer cells' sensitivity and response to each in vitro and in mice.
The 14 cell lines included two with mutations producing amplified levels of HER2. The researchers found that lapatinib had concentration-dependent antiproliferative effects across the cell lines, with the greatest effects in the two HER2-amplified cell lines. The combination of lapatinib and trastuzumab was found to have a greater antitumor efficacy than either drug alone in the HER2-amplified cells and in HER2-amplified xenograft mouse models.
"Lapatinib showed significant synergy when combined with trastuzumab in both of the HER2-amplified cell lines. Furthermore, in the N87 xenograft, the combination of lapatinib and trastuzumab induced a near complete tumor regression in all the mice that were treated. These effects were much more pronounced than either lapatinib or trastuzumab alone," the authors conclude.
Three study authors reported receiving research grants or serving on advisory boards for GlaxoSmithKline.
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