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Caveats for Interpretation Several caveats apply to all stack comparisons in preclinical research: "Pathway coverage" is a mechanistic abstraction, not a guarantee of combined effect Combination synergy must be demonstrated experimentally, not inferred Research outcomes depend heavily on the specific cell model and assay system None of these observations translate to medical or clinical applications Researchers using stacks should design experiments that can resolve the contributions of each component typically through four-arm designs (vehicle, each alone, both together) with dose-response characterization
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