Fig. 2
Drug inhibition and resistance mechanisms in dynamic network models. a The network model of Fig. 1a with additional nodes denoting a RTK inhibitor (RTKi) and a MEK inhibitor (MEKi). b-d Time courses of node activity (average node state) in response to Growth Factor (GF) in the presence of RTKi, a RAS activating mutation, and MEKi. For panel B, we start with an initial state in which the only active node is Growth Factor and there is no RTK inhibitor (σRTKi = OFF); we introduce the RTKi by setting σRTKi = ON for time ≥ 20. For panel C, we start with an initial state with σGF = σRTKi = ON and introduce a RAS activating mutation by setting fRAS = ON for time ≥ 20. For panel D, we start with an initial state with σGF = σRTKi = ON and with the modified function fRAS = ON, and introduce a MEK inhibitor by setting σMEKi = ON for time ≥ 20. Note that the time courses of the activity of several nodes overlap in panels c and d, in particular, PI3K and RAF, and PIP3 and MEK/ERK