Fig. 7
In vivo potency of trametinib against COSCC. (A, B) MRI images of tumor-bearing mice before and after treatment with trametinib. Tumors are shown in red. (C, D) MRI images of tumor-bearing mice before and after treatment with carrier control. Tumors are shown in red. (E) Mouse tumors were measured (length and width) with calipers twice a week. Tumor volume was estimated as 0.5 * width (shorter measurement) * width * length (longer measurement). The drug treatment began at 0.5 mg/kg but was increased to 0.75 mg/kg on day 12 (marked with ¥). Datapoints represent the mean value from all six mice in each group, with error bars representing the standard deviation from the mean. The * represents data for which the p-value between treated and untreated samples is < 0.05. The exact p-value for the first statistically significant datapoint is shown. (F) Individual growth curves for each mouse tumor. Curves are grouped into ‘vehicle’ (V) or ‘treated’ (T) groups. One mouse (V1, indicated with a red arrow) was treated only with carrier control, but had a comparatively slow growing tumor. (G) Individual tumors removed from untreated and trametinib treated mice. Tumors from untreated mice are substantially larger than those from treated mice. (H) The weights of tumors in (G) were determined. (I) The body weight of each mouse was determined immediately before drug was injected. Drug treatment had no noticeable impact on body weight, and untreated mice grew slightly heavier throughout the course of the experiment. (J) Individual body weight plots for each mouse. One mouse in the drug treated group (T5, indicated with red arrow) was consistently lighter than all other mice, and died of treatment complications on the final day of the experiment, resulting in desiccation and body weight loss. (K) The weight of each mouse’s tumor was subtracted from its total weight, and then the weights of the treated and untreated mice were compared. There is no statistical difference between their body weights on the final day of the experiment once tumor weights are controlled for.
