Curvature-based schedule ordering is preserved in homogeneous and heterogeneous tumors

Curvature-based ordering of equal-mean dosing schedules is preserved in heterogeneous tumors, even as treatment selection shifts surviving cells toward drug resistance.

• Why it matters: Identical total doses can favor different schedules depending on how exposure is timed, but it was unclear whether heterogeneous sensitivities and selection could flip that curvature-predicted preference.
• What they did: The authors build a mathematical framework where phenotypes share one concentration-effect function and differ only by fixed nonnegative sensitivity scales, then prove schedule ordering depends only on the scalar cumulative treatment effect.
• The result: Baseline heterogeneity and treatment-induced selection can change response magnitude and surviving-cell composition, but cannot reverse the curvature-predicted ordering across different temporal profiles and repeated treatment cycles.

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