Optimal control to reach eco-evolutionary stability in metastatic castrate-resistant prostate cancer.
Jessica J. Cunningham,Frank Thuijsman,Ralf Peeters,Yannick Viossat,Joel S. Brown,Robert A. Gatenby,Kateřina Staňková,Kateřina Staňková +7 more
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Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes.Abstract:
In the absence of curative therapies, treatment of metastatic castrate-resistant prostate cancer (mCRPC) using currently available drugs can be improved by integrating evolutionary principles that govern proliferation of resistant subpopulations into current treatment protocols. Here we develop what is coined as an ‘evolutionary stable therapy’, within the context of the mathematical model that has been used to inform the first adaptive therapy clinical trial of mCRPC. The objective of this therapy is to maintain a stable polymorphic tumor heterogeneity of sensitive and resistant cells to therapy in order to prolong treatment efficacy and progression free survival. Optimal control analysis shows that an increasing dose titration protocol, a very common clinical dosing process, can achieve tumor stabilization for a wide range of potential initial tumor compositions and volumes. Furthermore, larger tumor volumes may counter intuitively be more likely to be stabilized if sensitive cells dominate the tumor composition at time of initial treatment, suggesting a delay of initial treatment could prove beneficial. While it remains uncertain if metastatic disease in humans has the properties that allow it to be truly stabilized, the benefits of a dose titration protocol warrant additional pre-clinical and clinical investigations.read more
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Evolution and the Theory of Games
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Eight principles of Integrated Pest Management.
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The Contribution of Evolutionary Game Theory to Understanding and Treating Cancer
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TL;DR: It is suggested that cancer progression is an evolutionary competition between different cell types and therefore needs to be viewed as an evolutionary game and has medically useful implications that can inform and create a lockstep between empirical findings and mathematical modeling.
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Evolution-based mathematical models significantly prolong response to abiraterone in metastatic castrate-resistant prostate cancer and identify strategies to further improve outcomes
TL;DR: A pilot study in which abiraterone dosing is guided by evolution-informed mathematical models to delay onset of resistance in metastatic castrate-resistant prostate cancer patients, which significantly increases TTP and OS.
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The Hallmarks of Cancer as Ecologically Driven Phenotypes
TL;DR: In this paper, the authors discuss the parallels between populations of cancer cells and populations of individuals in the wild, highlighting how individuals in either context are constrained by their environments to converge on a small number of critical phenotypes to ensure survival and future reproductive success.
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