Dosage strategies for delaying resistance emergence in heterogeneous tumors

Vahideh Vakil, Wade Trappe

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


Drug resistance in cancer treatments is a frequent problem that, when it arises, leads to failure in therapeutic efforts. Tumor heterogeneity is the primary reason for resistance emergence and a precise treatment design that takes heterogeneity into account is required to postpone the rise of resistant subpopulations in the tumor environment. In this paper, we present a mathematical framework involving clonal evolution modeling of drug-sensitive and drug-resistant clones. Using our framework, we examine delaying the rise of resistance in heterogeneous tumors during control phase of therapy in a containment treatment approach. We apply pharmacokinetic/pharmacodynamic (PKPD) modeling and show that dosage strategies can be designed to control the resistant subpopulation. Our results show that the drug dosage and schedule determine the relative dynamics of sensitive and resistant clones. We present an optimal control problem that finds the dosing strategy that maximizes the delay in resistance emergence for a given period of containment treatment.

Original languageEnglish (US)
Pages (from-to)1322-1331
Number of pages10
JournalFEBS Open Bio
Issue number5
StatePublished - May 2021

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


  • clonal evolution
  • containment
  • dosage strategy
  • drug resistance
  • optimal control


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