FIG. 14.

(a) Signal is triggered and propagated along activation edges; (b) after TKI is introduced (short term), downstream components such as phospo- HER3, PI3K, Akt, and MAPK are regulated because TKI inhibits and regulates downstream components (positive negative feedback); and (c) for long-term behavior, even though a small triggering signal is introduced, the downstream components are not regulated but are activated because the biological network evolves to positive positive feedback (gray: not triggered edge; red: activation edge; blue: inhibition edge; light red/blue: deactivated edges after once activated).