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Updated: May 23, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Evolutionary Antifragile Therapy Is a Treatment Strategy to Suppress Drug Resistance by Exploiting Dose-Response

Jeffrey West1, Bina Desai2, Maximilian A R Strobl3

  • 1Integrated Mathematical Oncology Department, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.

Cancer Research
|May 22, 2026
PubMed

Insights

Tumor cells can be antifragile, benefiting from treatment fluctuations. Analyzing dose response curve convexity predicts treatment effectiveness, guiding "Evolutionary Antifragile Therapy" to limit resistance.

Area of Science:

  • Oncology
  • Mathematical Biology
  • Evolutionary Medicine

Background:

  • Tumor cell populations can exhibit antifragility, gaining benefits from treatment-induced environmental fluctuations.
  • Treatment fluctuations can either promote or inhibit the evolution of treatment resistance to targeted therapies.

Purpose of the Study:

  • To investigate how dose response curve convexity predicts tumor response to fluctuating treatment schedules.
  • To explore the concept of "Evolutionary Antifragile Therapy" for limiting treatment resistance.

Main Methods:

  • Analysis of dose response curve convexity to predict treatment outcomes.
  • Experimental validation using intermittent versus continuous dosing schedules in vivo.
  • Mathematical modeling of tumor evolution under varying treatment regimens.

Main Results:

  • Convexity of dose response curves accurately predicted that continuous treatment outperforms uneven protocols for convex responses.
  • Dose response was identified as a convex (fragile) function, while resistance onset rate was concave (antifragile).
  • Fluctuating treatment schedules, designed using dose response curvature analysis, maximized response and prolonged sensitivity.

Conclusions:

  • Treatment fluctuations significantly alter tumor evolutionary trajectories, even without changing cumulative dose.
  • Understanding dose response curvature is key to designing "Evolutionary Antifragile Therapy" protocols.
  • This approach offers a strategy to limit the evolution of resistance in targeted cancer therapies.

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