Extended Data Fig. 17: Model calculated and experimentally determined DPD responses of SKMEL-133 cells to different inhibitors.

(A) The experimentally measured DPD values (dots) are calculated based on the data from the reference Korkut et al.²⁹. Model-predicted (blue curves) DPD responses to many inhibitors exhibit abrupt DPD decreases at certain inhibitor doses caused by the loss of stability of a proliferation state and the induction of apoptosis in a threshold manner. Mathematically, an abrupt DPD decrease relates to a saddle-node bifurcation⁶³ (a fold catastrophe) that occurs when a stable steady-state solution corresponding to a proliferation state disappears. Data are presented as mean values +/− SEM for n = 3 biologically independent experiments. (B) Synergy between MEK/ERK and PI3K/AKT inhibitors is demonstrated by concave Loewe isoboles.