State-gating strategies to control cancer cell plasticity by remodeling the cancer landscape. A, A subspace of the cancer cell state landscape containing epithelial (E) and hybrid epithelial/mesenchymal (E/M) attractor states linked by plastic transitions. B, Chemotherapy (Chemo) remodels the landscape favoring the transition from the E to the E/M state while inhibiting the reverse process. This increases the population of E/M cells, which promote metastasis and therapy resistance. C–E, Potential antiplasticity state-gating strategies: activating E/M-to-E transition (C), inhibiting E-to-E/M transition (D), and inhibiting E/M self-renewal (E). These will have dual actions, preventing the amplification of E/M cells by chemotherapy while favoring the E state that is sensitive to chemotherapy.