Figure 8.

Schematic depicting dynamical traits of coupled EMT-ERα signaling network and its implications in tumor survival. (A) Landscape showing multiple phenotypes defined on EMT and drug resistance axes: ES (epithelial-sensitive) and MR (mesenchymal-resistant) phenotypes are more dominant (witnessed by depth of the valley in the landscape). Arrows induced transitions under the influence of noise or drug among six phenotypes (ES, ER, HS, HR, MS, MR). (B) Population dynamics showing multiple parallel paths to long-term resistance (pre-existing reversibly resistant cells, stochastic switching and dynamic equilibrium, and drug-induced plasticity) and the predicted effect of combinatorial therapy (anti-estrogen therapy + MET inducers) to drive population collapse.