Figure 1
Schematic representation of the integrated semimechanistic PK/PD model describing (A) vemurafenib-meditated efficacy under non-resistant conditions through inhibition of the MAPK pathway and the cell cycle, and (B) acquisition of resistance to vemurafenib by the upregulation of the MAPK pathway and abemaciclib-mediated efficacy through cell cycle arrest and increased dependence on Total Rb for survival. Arrowheads denote positive relationships, flatheads denote negative relationships. Red arrows indicate route of efficacy; purple arrows indicate elevation of baseline biomarker levels as a result of vemurafenib resistance. Shaded boxes denote observed compartments. Parameters are defined in the text.
