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The value of monitoring to control evolving populations.
Fischer, Andrej; Vázquez-García, Ignacio; Mustonen, Ville.
Affiliation
  • Fischer A; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; and.
  • Vázquez-García I; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; and Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge CB3 0WA, United Kingdom.
  • Mustonen V; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, United Kingdom; and vm5@sanger.ac.uk.
Proc Natl Acad Sci U S A ; 112(4): 1007-12, 2015 Jan 27.
Article in En | MEDLINE | ID: mdl-25587136
Populations can evolve to adapt to external changes. The capacity to evolve and adapt makes successful treatment of infectious diseases and cancer difficult. Indeed, therapy resistance has become a key challenge for global health. Therefore, ideas of how to control evolving populations to overcome this threat are valuable. Here we use the mathematical concepts of stochastic optimal control to study what is needed to control evolving populations. Following established routes to calculate control strategies, we first study how a polymorphism can be maintained in a finite population by adaptively tuning selection. We then introduce a minimal model of drug resistance in a stochastically evolving cancer cell population and compute adaptive therapies. When decisions are in this manner based on monitoring the response of the tumor, this can outperform established therapy paradigms. For both case studies, we demonstrate the importance of high-resolution monitoring of the target population to achieve a given control objective, thus quantifying the intuition that to control, one must monitor.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Resistance, Neoplasm / Models, Biological / Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2015 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Drug Resistance, Neoplasm / Models, Biological / Neoplasms Type of study: Prognostic_studies Limits: Humans Language: En Journal: Proc Natl Acad Sci U S A Year: 2015 Document type: Article Country of publication: United States