Metastasis suppression by high-dose, multi-drug targeting is unsuccessful due to network
heterogeneity and compensatory network activation. Here, we show that targeting driver
network signaling capacity by limited inhibition of core pathways is a more effective anti-
metastatic strategy. This principle underlies the action of a physiological metastasis
suppressor, Raf Kinase Inhibitory Protein (RKIP), that moderately decreases stress-
regulated MAP kinase network activity, reducing output to transcription factors such as pro …

Metastasis suppression by high-dose, multi-drug targeting is largely unsuccessful due to
network heterogeneity and compensatory network activation. Here we show that targeting
driver network signaling capacity by limited inhibition of its core pathways is a more effective
anti-metastatic strategy. This principle underlies the action of a physiological metastasis
suppressor, Raf Kinase Inhibitory Protein, which moderately decreases stress-regulated
MAP kinase network activity, reducing the output to metastatic transcription factor BACH1 …