Independent proof domains and translational readouts establishing architectural collapse across biological and clinical scales.
Architectural Oncology advances claims about architecture-wide feasibility and collapse. Such claims require evidence that generalizes beyond any single assay, model, or experimental context. No single readout is sufficient: architectural collapse is established only when convergent signals are observed across independent, orthogonal biological and translational settings.
Proof Domains
Proof domains are independent experimental contexts in which architectural feasibility and collapse can be tested without relying on shared assumptions or measurement artifacts.
They span multiple levels of biological organization, including cellular systems under sustained oncogenic load, tissue-level models that preserve structural coordination, and in vivo contexts where execution must be maintained across physiological constraints and over time.
Across domains, a collapse signature (loss of executability) must be reproducible and non-compensable.
Structural Translational Metrics
Conventional translational metrics focus on target engagement, pathway suppression, or tumor burden. While informative, these measures do not directly assess architectural feasibility.
Structural translational metrics instead capture architecture-level consequences of perturbation, including loss of coordination across execution domains, reduced tolerance to oncogenic load, and failure to sustain organized cellular execution under stress.
These metrics bridge findings across model systems and preserve architectural meaning as investigations progress toward clinical evaluation.
Clinical Readouts of Architectural Collapse
Clinical evaluation focuses on whether therapeutic perturbation produces interpretable architecture-wide effects in patients. Readouts are selected to reflect feasibility loss rather than isolated molecular response.
This includes assessing whether malignant persistence becomes non-executable under therapeutic pressure, whether this loss is sustained rather than transient, and whether the observed pattern is consistent with architectural collapse rather than nonspecific suppression.
Clinical signals are interpreted conservatively and integrated with supporting evidence from non-clinical proof domains.