Dabrafenib; Preclinical Characterization, Increased Efficacy when Combined with Trametinib, while BRAF/MEK Tool Combination Reduced Skin Lesions
Figure 4
Modulation of pharmacodynamic markers by dabrafenib in BRAFV600E tumors.
Mice bearing A375P tumor xenografts were treated orally with 30 mg/kg dabrafenib, once daily for 14 days. Blood and tumors from vehicle- and dabrafenib-treated animals were analyzed for compound concentration and pERK inhibition, respectively (A). Phospho-ERK (pERK) is normalized to total ERK (tERK). Tumors harvested 6h post-last 6th dose were stained for Ki67, p27, and ppERK by immunohistochemistry and compared with pre-treatment controls (B). Data are representative of n = 3 studies and percent changes were calculated from the ratio of positively stained cells following drug treatment to those following vehicle control treatment, each as a percentage of the total cell population.