A University of Colorado (CU) Cancer Center study published online on November 5, 2014 in Molecular Cancer Therapeutics reports anti-cancer activity in 10 of 11 patient tumor samples grown in mice and treated with the experimental drug TAK-733 (image), a small molecule inhibitor of MEK1/2. While the drug is conceived as a second-generation inhibitor in patients harboring the BRAF mutation, the study shows drug activity in melanoma models regardless of BRAF mutation status. Treated tumors shrunk up to 100 percent. “The importance of this molecule is that it’s a next-generation and highly potent inhibitor of a known melanoma pathway. It was highly effective against melanoma and the method of our study – using patient-derived tumor samples grown in mice – makes us especially optimistic that we should see similar results in the human disease,” says John Tentler, Ph.D., investigator at the CU Cancer Center, associate professor at the CU School of Medicine, and one of the paper’s lead authors. Between fifty and sixty percent of human melanomas have an activating mutation in the gene BRAF. According to National Cancer Institute statistics, approximately 1 million people in the United States live with melanoma at any given time. In 2011, the U.S. Food and Drug Administration approved the drug vemurafenib to treat BRAF-mutant melanoma. But while response rates to vemurafenib are in the range of 80 percent for patients with the BRAF mutation, the duration of response is frequently limited to between 2 and 18 months. “We’re learning how to use existing drugs better, for example RAF along with MEK inhibitors to block both mutations and thus a common mechanism of resistance.
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