Fig. 5.

Evolutionary-informed BRAF inhibitor dosing schedules outperform continuous or fixed intermittent dosing in vivo A. Treatment schema for mouse experiment comparing continuous and fixed intermittent schedule of BRAF inhibitor treatment to personalized, adaptive dosing using mathematical modelling of individual xenografted tumours. B. Evolutionary-informed adaptive dosing schedules are associated with better tumour control than either continuous or fixed intermittent drug dosing. Data show mean tumour volume data from WM164 melanoma xenografts between the three BRAF inhibitor treatment groups over time (left). Untreated “sentinel” mice receiving drug free chow is shown by the dotted line. Average tumour volumes are shown for each treatment group on the last day of the experiment (right). C. Mathematical modelling of tumour response dynamics under drug predicts individual dosing schedules for each mouse. Individual tumour volume and treatment data are shown from the adaptive treatment group over time (green line = off therapy, red line = on therapy). D. Chart shows individual dosing schedules for each mouse on the adaptive treatment arm of the xenograft experiment (grey: on therapy. White: off therapy), along with the increases in individual tumour volumes at the end of the experiment. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)